基质金属蛋白酶-26在非小细胞肺癌中的表达及其基因沉默对肺癌细胞生物学行为的影响
|
摘要
近年来肺癌的发病率和死亡率在世界范围内呈不断上升的趋势,其中80%表现为NSCLC。因此,从分子水平了解NSCLC侵袭与转移的过程,寻找可靠的标志物来预测患者复发或不良预后是目前国内外研究的热点。MMP-26广泛表达于正常和肿瘤组织,但在NSCLC中的表达及其生物学作用的研究尚未见报道。
本研究采用原位杂交、免疫组化、RT-PCR、Western blot和明胶酶谱分析等方法,检测了MMP-26及其特异性抑制因子TIMP-4在NSCLC组织和细胞中的表达情况;应用RNAi技术抑制MMP-26基因在人肺癌细胞中的表达,体外观察基因沉默对细胞生物学行为的影响,并对其作用机制进行初步探讨。
研究表明,MMP-26和TIMP-4在NSCLC组织中协同表达;MMP-26可能通过降解ECM或激活MMP-9参与NSCLC的早期侵袭过程,检测MMP-26的表达有助于预测NSCLC患者的预后;RNAi介导的MMP-26基因表达沉默可有效降低肺癌细胞浸润能力,其作用可能是通过与MMP-9的协调来实现的,故而MMP-26有望成为抗NSCLC侵袭的分子靶点。
随着MMP-26在肿瘤发生发展中作用研究的深入,MMP-26作为靶基因可能为肿瘤的治疗开辟新的有效途径,其具体应用价值还有待进一步探寻。
Lung cancer remains the most common cause of cancerrelated death in the world. Non-small cell lung cancer (NSCLC) accounts for appoximately 80% of all lung cancers. The 5-year survival of patients with NSCLC remains among the lowest of all major human cancers despite recent advances in surgical, radiation, and medical treaments. The majority of the dignosed patients with NSCLC died of local recurrence and distant metastasis. Therefore, there is intense interest in gaining a better understanding of the molecular and cellular processes involved in this aggressive disease and searching for reliable biomarkers to predict relapse and poor outcome.
MMP-26 is a recently discovered and only partially characterized human proteinase. It has several structural features of MMPs, including the signal sequence, the prodomain domain and the catalytic domain, but it lacks the hemopexin-like domain. A unique“cysteine switch”sequence in the prodomain, PHCGVPD as opposed to the conserved PRCGXXD sequence found in many other MMPs, keeps the enzyme latent. MMP-26 mRNA is specifically expressed in epithelial cancers, such as breast, endometrial and prostate carcinomas, in their corresponding cell lines and in normal adult tissues, such as the uterus, placenta and kidney. This protein hydrolyzes various components of the ECM, including fibronectin, type IV collagen, vitronectin and fibrinogen, as well as non-ECM proteins, indicating that MMP-26 is a potent enzyme with a wide substrate specificity. MMP-26 is also able to activate progelatinase B. These data suggest that MMP-26 may plays a key role in tumor progression. Previous studies have showed that TIMP-4 is most potent against MMP-26 compared with other MMPs tested. To date, detailed function and expression patterns of MMP-26 in NSCLC tissues and cells have not been reported. The aim of the study is to determine if MMP-26 may be responsible for the invasive and metastasis behaviour of NSCLC and to future investigate the mechanism of MMP-26 in tumor process.
The main methods of this study were as follows:
1. In situ hybridization was performed to identify MMP-26 and TIMP-4 mRNA location in NSCLC. MMP-26 and TIMP-4 expressions were determined in NSCLC tissues, paracancerous tissues and benign pulmonary diseases tissues by immunohistochemical technique. Furthermore, we studied the relationship between expression of MMP-26 and TIMP-4 proteins and clinic pathological feature in NSCLC. The expression of MMP-26 and MMP-9 were analyzed immunohisto- chemically in NSCLC tissues.
2. The expression levels of MMP-26 and TIMP-4 mRNAs and proteins in A549 cells and SPC-A-1 cells were detected by semi-quantitative reverse transcription- polymerase chain reaction (RT-PCR), Western blot and zymography.
3. MMP-26 mRNA targeted hairpin siRNA was devised and three pairs of oligonucleotides encoding the above siRNA were synthesized. After annealing of the complementary strands, the DNA fragments were inserted into plamid pSUPERIOR.puro to generate siRNA eukaryotic expression vectors, followed by amplificaton and DNA sequencing.
4. The recombinant plasmids were transiently transfected into A549 cells. The expression levels of MMP-26 mRNA and protein in A549 cells were detected by semi-quantitative RT-PCR, Western blot and immunfluorescence. A549 cells stably transfected with the recombinant plasmids were selected by puromycin.
5. The changes in cell morphology in routine and three-dimensional culture were observed under a light microscopy. MTT and colony forming assay were used to detect status of cell proliferation. Cell cycle of A549 cells after transfection was evaluated by flow cytometry. The adhesive, migratory and invasive abilities of A549 cells were measured via plate adhesion assay, cell scratch wound model and transwell chamber in vitro.
6. The expression levels of MMP-9 mRNA and protein were examined by semi- quantitative RT-PCR, Western blot and double immunofluorescent staining.
The main results of this study were as follows:
1. In situ hybridization signal localized MMP-26 predominantly in tumor cells and epithelial cells, but TIMP-4 mRNA in the same samples was present mainly in stromal cells.
2. There was strong MMP-26 staining of epithelial cells and cytoplasm of tumor cells in carcinoma tissues, but no general stromal staining was seen. In paracancerous lung tissues, weak immunoreactivity for MMP-26 was only occasionally observed in macrophages. The signal intensities of MMP-26 protein in NSCLC were significantly higher than those in benign pulmonary diseases tissues and paracancerous tissues (P<0.01). MMP-26 expression was significantly correlated with histopathology, cell differentiation and advanced TNM stage (P<0.05).
3. Immunostaining for TIMP-4 was present mainly in epithelial cells and cytoplasm of tumor cells in carcinoma tissues, and stroma had weakly staining. Immunohistochemistry for TIMP-4 protein was negative in paracancerous lung tissues. The signal intensities of TIMP-4 protein in NSCLC were significantly higher than those in benign pulmonary diseases tissues and paracancerous tissues (P<0.01). The expression of TIMP-4 showed no significance with all clinicobiological varies (P>0.05).
4. MMP-26 and MMP-9 proteins were both expressed in the same regions of NSCLC tissue samples.
5. MMP-26 mRNA and protein were expressed in these two NSCLC cell strains, but those of TIMP-4 were not detected.
6. The DNA fragments encoding MMP-26-targeted siRNA were cloned into the pSUPERIOR.puro and confirmed by restrictive enzyme digestion and DNA sequencing.
7. Semi-quantitative RT-PCR showed that the mRNA transcription of MMP-26 gene in A549 cells transfeced with the recombinant plasmid pshRNA-MMP26-C was reduced by nearly 65%. The expression of MMP-26 protein in pshRNA-MMP26-C group was significantly lower than that of other groups (P<0.01).
8. We obtained monocloned cell strains, which stably expressed siRNA-MMP26 after selection by puromycin. The results demonstrated that①The adhesive rate was down-regulated in pshRNA-MMP26-C group, when compared to the controls (P<0.05). Silencing of MMP-26 gene significantly retarded the invasiveness of A549 cells in transwell insert invasion assay (P<0.05).②All of the cells could proliferate in the three-dimensional culture system. A549 cells transfected with pshRNA-MMP26-C plasmid mainly developed reticular structure in morphology, and formed few clones with clear and smooth edges as well as tight intercellular junctions. Controls cells formed clones with irregular morphology, unclear edge, and loose intercellular junctions. In addition, the clones also developed a lot of pseudopodia, but developed no reticular structure.③Compared with the controls, other varies showed no difference statistically (P>0.05).
9. The mRNA and protein expression of MMP-9 in pshRNA-MMP26-C group were significantly lower than those of the controls (P<0.05). Double immuno- fluorescence labeling and focal laser scanning microscopy revealed that MMP-26 was colocalized with MMP-9 in the controls.
The main conclusions of this study are as follows:
1. MMP-26 may participate in NSCLC early invasive, either directly by degrading ECM or indirectly by activating pro-MMP-9.
2. Expression silencing of MMP-26 by RNAi could reduce invasion of lung carcinoma cells effectively, and it may function, at least in part, through coordination with MMP-9.
本研究采用原位杂交、免疫组化、RT-PCR、Western blot和明胶酶谱分析等方法,检测了MMP-26及其特异性抑制因子TIMP-4在NSCLC组织和细胞中的表达情况;应用RNAi技术抑制MMP-26基因在人肺癌细胞中的表达,体外观察基因沉默对细胞生物学行为的影响,并对其作用机制进行初步探讨。
研究表明,MMP-26和TIMP-4在NSCLC组织中协同表达;MMP-26可能通过降解ECM或激活MMP-9参与NSCLC的早期侵袭过程,检测MMP-26的表达有助于预测NSCLC患者的预后;RNAi介导的MMP-26基因表达沉默可有效降低肺癌细胞浸润能力,其作用可能是通过与MMP-9的协调来实现的,故而MMP-26有望成为抗NSCLC侵袭的分子靶点。
随着MMP-26在肿瘤发生发展中作用研究的深入,MMP-26作为靶基因可能为肿瘤的治疗开辟新的有效途径,其具体应用价值还有待进一步探寻。
Lung cancer remains the most common cause of cancerrelated death in the world. Non-small cell lung cancer (NSCLC) accounts for appoximately 80% of all lung cancers. The 5-year survival of patients with NSCLC remains among the lowest of all major human cancers despite recent advances in surgical, radiation, and medical treaments. The majority of the dignosed patients with NSCLC died of local recurrence and distant metastasis. Therefore, there is intense interest in gaining a better understanding of the molecular and cellular processes involved in this aggressive disease and searching for reliable biomarkers to predict relapse and poor outcome.
MMP-26 is a recently discovered and only partially characterized human proteinase. It has several structural features of MMPs, including the signal sequence, the prodomain domain and the catalytic domain, but it lacks the hemopexin-like domain. A unique“cysteine switch”sequence in the prodomain, PHCGVPD as opposed to the conserved PRCGXXD sequence found in many other MMPs, keeps the enzyme latent. MMP-26 mRNA is specifically expressed in epithelial cancers, such as breast, endometrial and prostate carcinomas, in their corresponding cell lines and in normal adult tissues, such as the uterus, placenta and kidney. This protein hydrolyzes various components of the ECM, including fibronectin, type IV collagen, vitronectin and fibrinogen, as well as non-ECM proteins, indicating that MMP-26 is a potent enzyme with a wide substrate specificity. MMP-26 is also able to activate progelatinase B. These data suggest that MMP-26 may plays a key role in tumor progression. Previous studies have showed that TIMP-4 is most potent against MMP-26 compared with other MMPs tested. To date, detailed function and expression patterns of MMP-26 in NSCLC tissues and cells have not been reported. The aim of the study is to determine if MMP-26 may be responsible for the invasive and metastasis behaviour of NSCLC and to future investigate the mechanism of MMP-26 in tumor process.
The main methods of this study were as follows:
1. In situ hybridization was performed to identify MMP-26 and TIMP-4 mRNA location in NSCLC. MMP-26 and TIMP-4 expressions were determined in NSCLC tissues, paracancerous tissues and benign pulmonary diseases tissues by immunohistochemical technique. Furthermore, we studied the relationship between expression of MMP-26 and TIMP-4 proteins and clinic pathological feature in NSCLC. The expression of MMP-26 and MMP-9 were analyzed immunohisto- chemically in NSCLC tissues.
2. The expression levels of MMP-26 and TIMP-4 mRNAs and proteins in A549 cells and SPC-A-1 cells were detected by semi-quantitative reverse transcription- polymerase chain reaction (RT-PCR), Western blot and zymography.
3. MMP-26 mRNA targeted hairpin siRNA was devised and three pairs of oligonucleotides encoding the above siRNA were synthesized. After annealing of the complementary strands, the DNA fragments were inserted into plamid pSUPERIOR.puro to generate siRNA eukaryotic expression vectors, followed by amplificaton and DNA sequencing.
4. The recombinant plasmids were transiently transfected into A549 cells. The expression levels of MMP-26 mRNA and protein in A549 cells were detected by semi-quantitative RT-PCR, Western blot and immunfluorescence. A549 cells stably transfected with the recombinant plasmids were selected by puromycin.
5. The changes in cell morphology in routine and three-dimensional culture were observed under a light microscopy. MTT and colony forming assay were used to detect status of cell proliferation. Cell cycle of A549 cells after transfection was evaluated by flow cytometry. The adhesive, migratory and invasive abilities of A549 cells were measured via plate adhesion assay, cell scratch wound model and transwell chamber in vitro.
6. The expression levels of MMP-9 mRNA and protein were examined by semi- quantitative RT-PCR, Western blot and double immunofluorescent staining.
The main results of this study were as follows:
1. In situ hybridization signal localized MMP-26 predominantly in tumor cells and epithelial cells, but TIMP-4 mRNA in the same samples was present mainly in stromal cells.
2. There was strong MMP-26 staining of epithelial cells and cytoplasm of tumor cells in carcinoma tissues, but no general stromal staining was seen. In paracancerous lung tissues, weak immunoreactivity for MMP-26 was only occasionally observed in macrophages. The signal intensities of MMP-26 protein in NSCLC were significantly higher than those in benign pulmonary diseases tissues and paracancerous tissues (P<0.01). MMP-26 expression was significantly correlated with histopathology, cell differentiation and advanced TNM stage (P<0.05).
3. Immunostaining for TIMP-4 was present mainly in epithelial cells and cytoplasm of tumor cells in carcinoma tissues, and stroma had weakly staining. Immunohistochemistry for TIMP-4 protein was negative in paracancerous lung tissues. The signal intensities of TIMP-4 protein in NSCLC were significantly higher than those in benign pulmonary diseases tissues and paracancerous tissues (P<0.01). The expression of TIMP-4 showed no significance with all clinicobiological varies (P>0.05).
4. MMP-26 and MMP-9 proteins were both expressed in the same regions of NSCLC tissue samples.
5. MMP-26 mRNA and protein were expressed in these two NSCLC cell strains, but those of TIMP-4 were not detected.
6. The DNA fragments encoding MMP-26-targeted siRNA were cloned into the pSUPERIOR.puro and confirmed by restrictive enzyme digestion and DNA sequencing.
7. Semi-quantitative RT-PCR showed that the mRNA transcription of MMP-26 gene in A549 cells transfeced with the recombinant plasmid pshRNA-MMP26-C was reduced by nearly 65%. The expression of MMP-26 protein in pshRNA-MMP26-C group was significantly lower than that of other groups (P<0.01).
8. We obtained monocloned cell strains, which stably expressed siRNA-MMP26 after selection by puromycin. The results demonstrated that①The adhesive rate was down-regulated in pshRNA-MMP26-C group, when compared to the controls (P<0.05). Silencing of MMP-26 gene significantly retarded the invasiveness of A549 cells in transwell insert invasion assay (P<0.05).②All of the cells could proliferate in the three-dimensional culture system. A549 cells transfected with pshRNA-MMP26-C plasmid mainly developed reticular structure in morphology, and formed few clones with clear and smooth edges as well as tight intercellular junctions. Controls cells formed clones with irregular morphology, unclear edge, and loose intercellular junctions. In addition, the clones also developed a lot of pseudopodia, but developed no reticular structure.③Compared with the controls, other varies showed no difference statistically (P>0.05).
9. The mRNA and protein expression of MMP-9 in pshRNA-MMP26-C group were significantly lower than those of the controls (P<0.05). Double immuno- fluorescence labeling and focal laser scanning microscopy revealed that MMP-26 was colocalized with MMP-9 in the controls.
The main conclusions of this study are as follows:
1. MMP-26 may participate in NSCLC early invasive, either directly by degrading ECM or indirectly by activating pro-MMP-9.
2. Expression silencing of MMP-26 by RNAi could reduce invasion of lung carcinoma cells effectively, and it may function, at least in part, through coordination with MMP-9.
引文
1.Malemud CJ. Matrix metalloproteinases (MMPs) in health and disease: an overview[J]. Front Biosci, 2006, 11:1696-1701
2.Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry[J]. Circ Res, 2003, 92 (8): 827-839
3.Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression [J]. Nat Rev Cancer, 2002, 2 (3):161-174
4.Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior[J]. Annu Rev Cell Dev Biol, 2001, 17: 463-516
5.Nagase H. Activation mechanisms of matrix metalloproteinases[J]. Biol Chem, 1997, 378 (3-4):151-160
6.Baker AH, Edwards DR, Murphy G. Metalloproteinase inhibitors: biological actions and therapeutic opportunities[J]. J Cell Sci, 2002, 115 (Pt 19): 3719-3727
7.Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function[J]. Biochim Biophys Acta, 2000, 1477 (1-2): 267-283
8.Nawrocki B, Polette M, Marchand V, et al. Expression of matrix metalloproteinases and their inhibitors in human bronchopulmonary carcinomas: quantificative and morphological analyses[J]. Int J Cancer, 1997, 72 (4): 556-564
9.Drac P, Klein J, Tichy T, et al. Prognostic impact of matrix metalloproteinases 2, 9, and 11 in stromal cells stage I non-small cell lung cancer[J]. Cas Lek Cesk, 2007, 146 (1): 45-47
10.Ishikawa S, Takenaka K, Yanagihara K, et al. Matrix metalloproteinase-2 status in stromal fibroblasts, not in tumor cells, is a significant prognostic factor in non-small-cell lung cancer[J]. Clin Cancer Res, 2004, 10 (19): 6579-6585
11.Kim SH, Choi HY, Lee J, et al. Elevated activities of MMP-2 in the non-tumorous lung tissues of curatively resected stage I NSCLC patients are associated with tumor recurrence and a poor survival[J]. J Surg Oncol, 2007, 95 (4): 337-346
12.Gill JH, Kirwan IG, Seargent JM, et al. MMP-10 is overexpressed, proteolytically active, and a potential target for therapeutic intervention in human lung carcinomas[J]. Neoplasia, 2004, 6 (6): 777-785
13.Galateau-Salle FB, Luna RE, Horiba K, et al. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in bronchial squamous preinvasive lesions[J]. Hum Patho1, 2000, 31 (3): 296-305
14.Thomas P, Khokha R, Shepherd FA, et al. Differential expression of matrix metallo- proteinases and their inhibitors in non-small cell lung cancer[J]. J Pathol, 2000, 190 (2): 150-156
15.Simi L, Andreani M, Davini F, et al. Simultaneous measurement of MMP9 and TIMP1 mRNA in human non small cell lung cancers by multiplex real time RT-PCR[J]. Lung Cancer, 2004, 45 (2): 171-179
16.Gouyer V, Conti M, Devos P. Tissue inhibitor of metalloproteinase 1 is an independent predictor of prognosis in patients with non-small cell lung carcinoma who undergo resection with curative intent[J]. Cancer, 2005, 103 (8): 1676-1684
17.Suzuki M, Iizasa T, Fujisawa T, et al. Expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases in non-small-cell lung cancer[J]. Invasion Metastasis, 1998-1999, 18 (3): 134-141
18.Pritchard SC, Nicolson MC, Lloret C, et al. Expression of matrix metallo- proteinases 1, 2, 9 and their tissue inhibitors in stage II non-small cell lung cancer: implications for MMP inhibition therapy[J]. Oncol Rep, 2001, 8 (2): 421-424
19.Cox G, Jones JL, Andi A, et al. A biological staging model for operable non-small cell lung cancer[J]. Thorax, 2001, 56 (7): 561-566
20.Delebecq TJ, Porte H, Zerimech F, et al. Overexpression level of stromelysin 3 is related to the lymph node involvement in non-small cell lung cancer[J]. Clin Cancer Res, 2000, 6 (3): 1086-1092
21.Kren L, Goncharuk VN, Krenova Z, et al. Expression of matrix metalloproteinases 3, 10 and 11 (stromelysins 1, 2 and 3) and matrix metalloproteinase 7 (matrilysin) by cancer cells in non-small cell lung neoplasms. Clinicopathologic studies[J]. Cesk Patol, 2006, 42 (1): 16-19
22.Sasaki H, Yukiue H, Moiriyama S, et al. Clinical significance of matrix metalloproteinase-7 and Ets-1 gene expression in patients with lung cancer[J]. J Surg Res, 2001, 101 (2): 242-247
23.Byun JH, Lee MA, Roh SY, et al. Association between cyclooxygenase-2 and matrix metalloproteinase-2 expression in non-small cell lung cancer[J]. Jpn J Clin Oncol, 2006, 36 (5): 263-268
24.Yamamura T, Nakanishi K, Hiroi S, et al. Expression of membrane- type-1- matrix metallo- proteinase and metalloproteinase-2 in nonsmall cell lung carcinomas[J]. Lung Cancer, 2002, 35 (3): 249-255
25.Pinto CA, Carvalho PE, Antonangelo L, et al. Morphometric evaluation of tumor matrix metaloproteinase 9 predicts survival after surgical resection of adeno-carcinoma of the lung[J]. Clin Cancer Res, 2003, 9 (8): 3098-3104
26.Leinonen T, Pirinen R, Bohm J, et al. Expression of matrix metalloproteinases 7 and 9 in non-small cell lung cancer. Relation to clinicopathological factors, beta-catenin and prognosis[J]. Lung Cancer, 2006, 51 (3): 313-321
27.Hofmann HS, Bartling B, Simm A, et al. Identification and classification of differentially expressed genes in non-small cell lung cancer by expression profiling on a global human
59.620-element oligonucleotide array[J]. Oncol Rep, 2006, 16 (3): 587-595
28.Aljada IS, Ramnath N, Donohue K, et al. Upregulation of the tissue inhibitor of metallo- proteinase-1 protein is associated with progression of human non-small cell lung cancer[J]. J Clin Oncol, 2004, 22 (16): 3218-3229
29.Mino N, Takenaka K, Sonobe M, et al. Expression of tissue inhibitor of metalloproteinase-3 (TIMP-3) and its prognostic significance in resected non-small cell lung cancer[J]. J Surg Oncol, 2007, 95 (3): 250-257
30.Herbst RS, Yano S, Kuniyasu H, et al. Differential expression of E-cadherin and type IV collagenase genes predicts outcome in patients with stage I non-small cell lung carcinoma[J]. Clin Cancer Res, 2000, 6 (3): 790-797
31.Fujise N, Nanashim A, Taniguchi Y, et al. Prognostic impact of cathepsin B and matrix metalloproteinase-9 in pulmonary adenocarcinomas by immunohistochemical study[J]. Lung Cancer, 2000, 27 (1): 19-26
32.Yamaguchi NH, Lichtenfels AJ, Demarchi LM, et al. COX-2, MMP-9, and Noguchi classification provide additional prognostic information about adenocarcinoma of the lung. A study of 117 patients from Brazil[J]. Am J Clin Pathol, 2004, 121 (1): 78-86
33.Swinson DE, Cox G, O' Byrne KJ, et al. Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non- small-cell lung cancer[J]. Br J Cancer, 2004, 91 (7): 1301-1307
34.王静, 苗丽君, 吴逸明, 等. 非小细胞肺癌组织中AKT2、Cyclin D1、MMP-9表达及其 与临床病理因素的关系[J]. 癌症, 2006, 25 (1): 69-72
35.Ferrigan L, Wallace WA. Predicting non-small cell lung cancer expression of epidermal growth factor receptor and matrix metalloproteinase 9 from immunohistochemical staining of diagnostic biopsy samples[J]. Eur J Cancer, 2004, 40 (10): 1589-1592
36.Mari BP, Anderson IC, Mari SE, et al. Stromelysin-3 is induced in tumor/stroma coculturesand inactivated via a tumor-specific and basic fibroblast growth factor-dependent mechanism[J]. J Biol Chem, 1998, 273 (1): 618-626
37.Gonzalez-Avila G, Iturria C, Vadillo F, et al. 72-kD (MMP-2) and 92-kD (MMP-9) type IV collagenase production and activity in different histologic types of lung cancer cells[J]. Pathobiology, 1998, 66 (1): 5-16
38.Lizasa T, Fujisawa T, Suzuki M, et al. Elevated levels of circulating plasma matrix metallo- proteinase 9 in non-small cell lung cancer patients[J]. Clin Cancer Res, 1999, 5(1):149-153
39.Ylisirnio S, Hoyhtya M, Turpeenniemi-Hujanen T. Serum MMP-2, -9 and TIMP-1, -2 in lung cancer-TIMP-1 as a prognostic marker[J]. Anticancer Res, 2000, 20 (2B): 1311-1316
40.Laack E, Kohler A, Kugler C, et al. Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer[J]. Ann Oncol, 2002, 13 (10): 1550-1557
41.Bugdayci G, Kaplan T, Sezer S, et al. Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer[J]. Exp Oncol, 2006, 28 (2): 169-171
42.Hrabec E, Strek M, Nowak D, et al. Elevated level of circulating matrix metalloproteinase-9 in patients with lung cancer[J]. Respir Med, 2001, 95 (1): 1-4
43.Susskind H, Hymowitz MH, Lau YH, et al. Increased plasma levels of matrix metallo- proteinase-9 and tissue inhibitor of metalloproteinase-1 in lung and breast cancer are altered during chest radiotherapy[J]. Int J Radiat Oncol Biol Phys, 2003, 56 (4): 1161-1169
44.Koc M, Ediger D, Budak F, et al. Matrix metalloproteinase-9 (MMP-9) elevated in serum but not in bronchial lavage fluid in patients with lung cancer[J]. Tumori, 2006, 92 (2): 149-154
45.Tamura M, Oda M, Matsumoto I, et al. The combination assay with circulating vascular endothelial growth factor (VEGF)-C, matrix metalloproteinase-9, and VEGF for diagnosing lymph node metastasis in patients with non-small cell lung cancer[J]. Ann Surg Oncol, 2004, 11 (10): 928-933
46.Laack E, Scheffler A, Burkholder I, et al. Pretreatment vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) serum levels in patients with metastatic non-small cell lung cancer (NSCLC)[J]. Lung Cancer, 2005, 50 (1): 51-58
47.赵军, 刘叙仪, 张青, 等. 晚期非小细胞肺癌患者外周血 VEGF 和 bFGF 及 MMP-9 水平与预后的关系[J]. 中华肿瘤杂志, 2005, 27 (11): 676-679
48.Yang SF, Hsieh YS, Lin CL, et al. Increased plasma levels of urokinase plasminogen activator and matrix metalloproteinase-9 in nonsmall cell lung cancer patients[J]. Clin ChimActa, 2005, 354 (1-2): 91-99
49.Eickelberg O, Sommerfeld CO, Wyser C, et al. MMP and TIMP expression pattern in pleural effusions of different origins[J]. Am J Respir Crit Care Med, 1997, 156 (6): 1987-1992
50. Di Carlo A, Terracciano D, Mariano A, et al. Matrix metalloproteinase-2 and matrix metalloproteinase-9 type IV collagenases in serum of patients with pleural effusions[J]. Int J Oncol, 2005, 26 (5): 1363-1368
51.Jin HY, Lee KS, Jin SM, et al. Vascular endothelial growth factor correlates with matrix metalloproteinase-9 in the pleural effusion[J]. Respir Med, 2004, 98 (2): 115-122
52.Reichenberger F, Eickelberg O, Wyser C, et al . Distinct endobronchial expression of matrix metalloproteinases (MMP) and their endogenous inhibitors in lung cancer[J]. Swiss Med Wkly, 2001, 131 (19-20): 273-279
53.Hakoda Y, Ito Y, Nagate A, et al. Increased collagenase activity in macrophages from brochial lavage as a diagnostic marker of non-small cell lung cancer[J]. Thorax, 2003, 58 (2): 122-126
54.Moses MA, Wiederschain D, Loughlin KR, et al. Increased incidence of matrix metallo- proteinases in urine of cancer patients[J]. Cancer Res, 1998, 58 (7): 1359-1399
55.Durkan GC, Nutt JE, Rajjayabun PH, et al. Prognostic significance of matrix metallo- proteinase-1 and tissue inhibitor of metalloproteinase-1 in voided urine samples from patients with transitional cell carcinoma of the bladder[J]. Clin Cancer Res, 2001, 7 (11): 3450-3456
56.Giavazzi R, Taraboletti G. Preclinical development of metalloproteasis inhibitors in cancer therapy[J]. Crit Rev Oncol Hematol, 2001, 37 (1): 53-60
57.Shinoda K, ShibuyaM, Hibino S, et al. A novel matrix metalloproteinase inhibitor, FYK 21388 suppresses tumor growth, metastasis and angiogenesis by human fibrosarcoma cell line[J]. Int J Oncol, 2003, 22 (2): 281-288
58.Fujino H, Kondo K, Ishikura H, et al. Matrix metalloproteinase inhibitor MMI-166 inhibits lymphogenous metastasis in an orthotopically implanted model of lung cancer[J]. Mol Cancer Ther, 2005, 4 (9): 1409-1416
59.Santos MA, Enyedy EA, Nuti E, et al. Methotrexate gamma-hydroxamate derivatives as potential dual target antitumor drugs[J]. Bioorg Med Chem, 2007, 15 (3): 1266-1274
60.Shepherd FA, Giaccone G, Seymour L, et al. Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to first-line chemo-therapy in patientswith small-cell lung cancer: a trial of the National Cancer Institute of Canada -Clinical Trials Group and the European Organization for Research and Treatment of Cancer[J]. J Clin Oncol, 2002, 20 (22): 4434-4439
61.Douillard JY, Peschel C, Shepherd F, et al. Randomized phase II feasibility study of combining the matrix metalloproteinase inhibitor BMS-275291 with paclitaxel plus carbo- platin in advanced non-small cell lung cancer[J]. Lung Cancer, 2004, 46 (3): 361-368
62.Itoh T, Tanioka M, Yoshida H, et al. Reduced angiogenesis and tumor progression in gelatinase A-deficient mice[J]. Cancer Res, 1998, 58 (5): 1048-1051
63.Li H, Lindenmeyer F, Grenet C, et al. Ad TIMP-2 inhibits tumor growth, angiogenesis, and metastasis, and prolongs survival in mice[J]. Hum Gene Ther, 2001, 12 (5): 515-526
64.孙建新, 张从昕, 殷学平, 等. 重组金属蛋白酶抑制因子-3 抗肿瘤作用的实验研究[J]. 中华肿瘤杂志, 1998, 20 (4): 10-12
65.Park HI, Ni J, Gerkema FE, et al. Identification and characterization of human endometase (Matrix metalloproteinase-26) from endometrial tumor[J]. J Biol Chem, 2000, 275 (27): 20540-20544
66.Uria JA, Lopez-Otin C. Matrilysin-2, a new matrix metalloproteinase expressed in human tumors and showing the minimal domain organization required for secretion, latency, and activity[J]. Cancer Res, 2000, 60 (17): 4745-4751
67.de Coignac AB, Elson G, Delneste Y, et al. Cloning of MMP-26. A novel matrilysin-like proteinase[J]. Eur J Biochem, 2000, 267 (11): 3323-3329
68.Mattei MG, Roeckel N, Olsen BR, et al. Genes of the membrane-type matrix metallo- proteinase (MT-MMP) gene family, MMP14, MMP15, and MMP16, localize to human chromosomes 14, 16, and 8, respectively[J]. Genomics, 1997, 40 (1): 168-169
69.Marchenko GN, Ratnikov BI, Rozanov DV, et al. Characterization of matrix metallo- proteinase-26, a novel metalloproteinase widely expressed in cancer cells of epithelial origin[J]. Biochem J, 2001, 356 (Pt 3): 705-718
70.Marchenko ND, Marchenko GN, Strongin AY. Unconventional activation mechanisms of MMP-26, a human matrix metalloproteinase with a unique PHCGXXD cysteine-switch motif[J]. J Biol Chem, 2002, 277 (21): 18967-18972
71.Park HI, Turk BE, Gerkema FE, et al. Peptide substrate specificities and protein cleavage sites of human endometase/ matrilysin-2/ matrix metalloproteinase-26[J]. J Biol Chem, 2002, 277 (38): 35168-35175
72.Park HI, Jin Y, Hurst DR, et al. The intermediate S1' pocket of the endometase/matrilysin-2active site revealed by enzyme inhibition kinetic studies, protein sequence analyses, and homology modeling[J]. J Biol Chem, 2003, 278 (51): 51646-51653
73.Lee S, Park HI, Sang QX. Calcium regulates tertiary structure and enzymatic activity of human endometase/matrilysin-2 and its role in promoting human breast cancer cell invasion[J]. Biochem J, 2006 Dec 18
74.Marchenko GN, Marchenko ND, Leng J, et al. Promoter characterization of the novel human matrix metalloproteinase-26 gene: regulation by the T-cell factor-4 implies specific expression of the gene in cancer cells of epithelial origin[J]. Biochem J, 2002, 363 (Pt 2): 253-262
75.Marchenko ND, Marchenko GN, Weinreb RN, et al. Beta-catenin regulates the gene of MMP-26, a novel metalloproteinase expressed both in carcinomas and normal epithelial cells[J]. Int J Biochem Cell Biol, 2004, 36 (5): 942-956
76.Shaulian E, Karin M. AP-1 as a regulator of cell life and death[J].Nat Cell Biol, 2002, 4 (5): 131-136
77.Pilka R, Whatling C, Domanski H, et al. Epithelial expression of matrix metallo- proteinase-26 is elevated at mid-cycle in the human endometrium[J]. Mol Hum Reprod, 2003, 9 (5): 271-277
78.Li W, Savinov AY, Rozanov DV, et al. Matrix metalloproteinase-26 is associated with estrogen-dependent malignancies and targets alpha1-antitrypsin serpin[J]. Cancer Res, 2004, 64 (23): 8657-8665
79.Pilka R, Norata GD, Domanski H, et al. Matrix metalloproteinase-26 (matrilysin-2) expression is high in endometrial hyperplasia and decreases with loss of histological differentiation in endometrial cancer[J]. Gynecol Oncol, 2004, 94 (3): 661-670
80.Pilka R, Domanski H, Hansson S, et al. Endometrial TIMP-4 mRNA is high at midcycle and in hyperplasia, but down-regulated in malignant tumours. Coordinated expression with MMP-26[J]. Mol Hum Reprod, 2004, 10 (9): 641-650
81. Pilka R, Kudela M, Eriksson P, et al. MMP-26 mRNA and estrogen receptor alpha co-expression in normal and pathological endometrium[J]. Ceska Gynekol, 2005, 70 (1): 56-62
82.关立华, 魏力, 张淑兰. MMP-26 和 TIMP-4 在人正常月经周期中的表达[J]. 现代妇产科进展, 2006, 15 (11): 826-829
83.Savinov AY, Remacle AG, Golubkov VS, et al. Matrix metalloproteinase 26 proteolysis of the NH2-terminal domain of the estrogen receptor beta correlates with the survival of breastcancer patients[J]. Cancer Res, 2006, 66 (5): 2716-2724
84.Liu YE, Wang M, Greene J, et al. Preparation and characterization of recombinant tissue inhibitor of metalloproteinase-4 (TIMP-4)[J]. J Biol Chem, 1997, 272 (33): 20479-20483
85.Zhang J, Cao YJ, Zhao YG, et al. Expression of matrix metalloproteinase-26 and tissue inhibitor of metalloproteinase-4 in human normal cytotrophoblast cells and a choriocarcinoma cell line,JEC-3[J]. Mol Hum Reprod, 2002, 8 (7): 659-666
86.Zhao YG, Xiao AZ, Park HI, et al. Endometase/matrilysin-2 in human breast ductal carcinoma in situ and its inhibition by tissue inhibitors of metalloproteinases-2 and -4: a putative role in the initiation of breast cancer invasion[J]. Cancer Res, 2004, 64 (2): 590-598
87.Bar-Or A, Nuttall RK, Duddy M, et al. Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis[J]. Brain, 2003, 126 (Pt 12): 2738-2749
88.Goffin F, Munaut C, Frankenne F, et al. Expression pattern of metalloproteinases and tissue inhibitors of matrix-metalloproteinases in cycling human endometrium[J]. Biol Reprod, 2003, 69 (3): 976-984
89.Chegini N, Rhoton-Vlasak A, Williams RS. Expression of matrix metalloproteinase-26 and tissue inhibitor of matrix metalloproteinase-3 and -4 in endometrium throughout the normal menstrual cycle and alteration in users of levonorgestrel implants who experience irregular uterine bleeding[J]. Fertil Steril, 2003, 80 (3): 564-570
90.Pilka R, Noskova V, Domanski H, et al. Endometrial TIMP-4 mRNA is expressed in the stroma, while TIMP-4 protein accumulates in the epithelium and is released to the uterine fluid[J]. Mol Hum Reprod, 2006, 12 (8): 497-503
91.Pilka R, Oborna I, Lichnovsky V, et al. Endometrial expression of the estrogen-sensitive genes MMP-26 and TIMP-4 is altered by a substitution protocol without down-regulation in IVF patients[J]. Hum Reprod, 2006, 21 (12): 3146-3156
92.Pilka R, Kudela M, Hansson S, et al. MMP-26 expression in endometrial explants treated with estradiol and progesterone[J]. Ceska Gynekol, 2004, 69 (6): 467-471
93.郭志荣, 柏素霞, 张踞, 等. 基质金属蛋白酶-26 在正常妇女和子宫内膜异位症患者子宫内膜中的时空变化[J]. 生殖与避孕, 2003, 23 (4): 195-199
94.Mencaglia L. Hysteroscopy and adenocarcinoma[J]. Obstet Gynecol Clin North Am, 1995, 22 (3): 573-579
95.关立华, 张淑兰. MMP-26 在正常子宫内膜和子宫内膜癌组织中的表达[J]. 中华肿瘤防治杂志, 2006, 13 (9): 651-655
96.Tunuguntla R, Ripley D, Sang QX, et al. Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinases TIMP-3 and -4 in benign endometrium and endometrial cancer[J]. Gynecol Oncol, 2003, 89 (3): 453-459
97.Isaka K, Nishi H, Nakai H, et al. Matrix metalloproteinase-26 is expressed in human endometrium but not in endometrial carcinoma[J]. Cancer, 2003, 97 (1): 79-89
98.Li Q, Wang H, Zhao Y, et al. Identification and specific expression of matrix metallo- proteinase-26 in rhesus monkey endometrium during early pregnancy[J]. Mol Hum Reprod, 2002, 8 (10): 934-940
99.Qiu W, Bai SX, Zhao MR, et al. Spatio-temporal expression of matrix metallo- proteinase-26 in human placental trophoblasts and fetal red cells during normal placentation[J]. Biol Reprod, 2005, 72 (4): 954-959
100.仇巍, 赵亮, 柏素霞, 等. MMP-26 在人正常胎盘滋养层细胞中的表达及激活素 A 对其表达的调节[J]. 生物化学与生物物理进展, 2005, 32 (1): 25-32
101.赵亮, 尚涛, 王雁玲, 等. 基质金属蛋白酶-26 在妊娠早期和中期原代细胞滋养细胞中的表达[J]. 中华妇产科杂志, 2004, 39 (2): 117-119
102.Rebecca LJ, Lois AS, Zhao YC, et al. Expression of activin receptors, follistatin and betaglycan by human endometrial stromal cells; consistent with a role for activins during decidualization[J]. Mol Hum Reprod, 2002, 8 (4): 363-374
103.吴晓秋, 李玉侠, 付雅媛, 等. 基质金属蛋白酶 MMP-26 能有效促进人绒毛膜上皮癌细胞 JEG-3 浸润能力[J]. 2006, 33 (6): 524-530
104.Ripley D, Tunuguntla R, Susi L, et al. Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinase-3 and -4 in normal ovary and ovarian carcinoma[J]. Int J Gynecol Cancer, 2006, 16 (5): 1794-1800
105.Zhao YG, Xiao AZ, Newcomer RG, et al. Activation of pro-gelatinase B by endometase/ matrilysin-2 promotes invasion of human prostate cancer cells[J]. J Biol Chem, 2003, 278 (17): 15056-15064
106.王阳, 李伟, 李一雷, 等. 乳腺良、恶性病变组织中MMP-26蛋白的表达及其与ER的关系[J]. 临床与实验病理学杂志, 2006, 22 (2): 182-185
107.Lee S, Desai KK, Iczkowski KA, et al. Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor[J]. Cell Res, 2006, 16 (9): 750-758
108.Impola U, Uitto VJ, Hietanen J, et al. Differential expression of matrilysin-1 (MMP-7), 92 kD gelatinase (MMP-9), and metalloelastase (MMP-12) in oral verrucous and squamouscell cancer[J]. J Pathol, 2004, 202 (1): 14-22
109.Yamamoto H, Vinitketkumnuen A, Adachi Y, et al. Association of matrilysin-2 (MMP-26) expression with tumor progression and activation of MMP-9 in esophageal squamous cell carcinoma[J]. Carcinogenesis, 2004, 25 (12): 2353-2360
110.Bister VO, Salmela MT, Karjalainen-Lindsberg ML, et al. Differential expression of three matrix metalloproteinases, MMP-19, MMP-26, and MMP-28, in normal and inflamed intestine and colon cancer[J]. Dig Dis Sci, 2004, 49 (4): 653-661
111.Bister V, Salmela MT, Heikkila P, et al. Matrilysins-1 and -2 (MMP-7 and -26) and metalloelastase (MMP-12), unlike MMP-19, are up-regulated in necrotizing enterocolitis[J]. J Pediatr Gastroenterol Nutr, 2005, 40 (1): 60-66
112.Bister V, Kolho KL, Karikoski R, et al. Metalloelastase (MMP-12) is upregulated in the gut of pediatric patients with potential celiac disease and in type 1 diabetes[J]. Scand J Gastroenterol, 2005, 40 (12): 1413-1422
113.Ahokas K, Skoog T, Suomela S, et al. Matrilysin-2 (matrix metalloproteinase-26) is upregulated in keratinocytes during wound repair and early skin carcinogenesis[J]. J Invest Dermatol, 2005, 124 (4): 849-856
114.Vogt PM, Lehnhardt M, Wagner D, et al. Growth factors and insulin-like growth factor binding proteins in acute wound fluid[J].Growth Horm IGF Res,1998, 8(Suppl B):107-109
115.Van Mater D, Kolligs FT, Dlugosz AA, et al. Transient activation of beta- catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice[J]. Genes Dev, 2003, 17 (10): 1219-1224
116. Skoog T, Ahokas K, Orsmark C, et al. MMP-21 is expressed by macrophages and fibroblasts in vivo and in culture[J]. Exp Dermatol, 2006, 15 (10): 775-783
117.Pirila E, Korpi JT, Korkiamaki T, et al. Collagenase-2 (MMP-8) and matrilysin-2 (MMP-26) expression in human wounds of different etiologies[J]. Wound Repair Regen, 2007, 15 (1): 47-57
118.Kuivanen T, Ahokas K, Virolainen S, et al. MMP-21 is upregulated at early stages of melanoma progression but disappears with more aggressive phenotype[J]. Virchows Arch, 2005, 447 (6): 954-960
119.Emingil G, Kuula H, Sorsa T, et al. Gingival crevicular fluid matrix metalloproteinase-25 and -26 levels in periodontal disease[J]. J Periodontol, 2006, 77 (4): 664-671
120.李慧云, 吴增常. 五种基质金属蛋白酶基因在乳头状甲状腺癌中的表达[J]. 中华内分泌代谢杂志, 2003, 19 (6): 449-451
121.Ferlay J, Bray F, Pisani P, et a1. GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide, version 2.0. IARC CancerBase No.5 Lyon: IARC Press, 2004
122.Olson TM, Hirohata S, Ye J, et al. Cloning of the human tissue inhibitor of metallo- proteinase-4 gene (TIMP-4) and localization of the TIMP-4 and TIMP-4 genes to human chromosome 3p25 and mouse chromosome 6, respectively[J]. Genomics, 1998, 51 (1): 148-151
123.Greene J, Wang M, Liu YE, et al. Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4[J]. J Biol Chem, 1996, 271 (48): 30375-30380
124.Mountain CF. Revisions in the international system for staging lung cancer[J]. Chest, 1997, 111 (6): 1710-1717
125.Tseng JE, Kemp BL, Khuri FR, et al. Loss of Fhit is frequent in stage I non-small cell lung cancer and in the lungs of chronic smokers[J]. Cancer Res, 1999, 59 (19): 4798-4803
126.Martini N, Flehinger BJ, Zaman MB, et al. Prospective study of 445 lung carcinomas with mediastinal lymph node metastases[J]. J Thorac Cardiovasc Surg, 1980, 80 (3): 390-399
127.Balbin M, Fueyo A, Tester AM, et al. Loss of collagenase-2 confers increased skin tumor susceptibility to male mice[J]. Nat Genet, 2003, 35 (3): 252-257
128.Polakis P. Wnt signaling and cancer[J]. Genes Dev, 2000, 14 (15): 1837-1851
129.Barker N, Clevers H. Catenins, Wnt signaling and cancer[J]. Bioessays, 2000, 22 (11): 961-965
130.Szabo E, Riffe ME, Steinberg SM, et al. Altered cJUN expression: an early event in human lung carcinogenesis[J]. Cancer Res, 1996, 56 (2): 305-315
131.Volm M, van Kaick G, Mattern J. Analysis of c-fos, c-jun, c-erbB1, c-erbB2 and c-myc in primary lung carcinomas and their lymph node metastases[J]. Clin Exp Metastasis, 1994, 12 (4): 329-334
132. Ramer R, Eichele K, Hinz B. Upregulation of tissue inhibitor of matrix metallo- proteinases-1 confers the anti-invasive action of cisplatin on human cancer cells[J]. Oncogene, 2007, Mar 19
133.Desmard M, Amara N, Lanone S, et al. Carbon monoxide reduces the expression and activity of matrix metalloproteinases 1 and 2 in alveolar epithelial cells[J]. Cell Mol Biol, 2005, 51 (4): 403-408
134.Hoshino Y, Mio T, Nagai S, et al. Fibrogenic and inflammatory cytokines modulate mRNA expressions of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-3 in type II pneumocytes[J]. Respiration, 2001, 68 (5): 509-516
135.Elbashir SM, Martinez J, Patkaniowska A, et al. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate[J]. EMBO J, 2001, 20 (23): 6877-6888
136.Schor SL, Schor AM, Winn B, et al. The use of three-dimensional collagen gels for the study of tumor cell invasion in vitro: experimental parameters influencing cell migration into the gel matrix[J]. Int J Cancer, 1982, 29 (1): 57-62
137.Fire A, Xu S, Montgomery M K, et al. Potent and specific genetic interference by double- stranded RNA in Caenorhabduis elegans[J]. Nature, 1998, 391 (6669): 806-811
138.Ramaswamy G, Slack FJ. SiRNA: A guide for RNA silencing[J]. Chem Biol, 2002, 9 (10): 1053-1055
139.Hannon GJ. RNA interference[J]. Nature, 2002, 418 (6894): 244-251
140.Yu JY, DeRuiter SL, Turner DL. RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells[J]. Proc Natl Acad Sci USA, 2002, 99 (9): 6047-60052
141.Yang D, Buchholz F, Huang Z, et al. Short RNA duplexes produced by hydrolysis with Escherichia coli RNase III mediate effective RNA interference in mammalian cells[J]. Proc Natl Acad Sci USA, 2002, 99 (15): 9942-9947
142.Sui G, Soohoo C, Afar EB, et al. A DNA vector-based RNAi technology to suppress gene expression in mammalian cells[J]. Proc Natl Acad Sci USA, 2002, 99 (8): 5515-5520
143.Castanotto D, Li H, Rossi JJ. Functional siRNA expression from transfected PCR products[J]. RNA, 2002, 8 (11): 1454-1460
144.Hannon GJ, Chubb A, Maroney PA, et al. Multiple cis-acting elements are required for RNA polymerase III transcription of the gene encoding H1 RNA, the RNA component of human RNase P[J]. J Biol Chem, 1991, 266 (34): 22796-22799
145.J萨姆布鲁克, D.W. 拉塞尔著. 黄培堂译. 分子克隆实验指南: 第 3 版[M]. 北京: 科学出版社, 2002, 1276-1305
146.Liotta LA. Tumor invasion and metastases--role of the extracellular matrix : Rhoads Memorial Award lecture[J]. Cancer Res, 1986, 46 (1): 1-7
147.Rao JS, Gondi C, Chetty C, et al. Inhibition of invasion, angiogenesis, tumor growth, and metastasis by adenovirus-mediated transfer of antisense uPAR and MMP-9 in non-small cell lung cancer cells[J]. Mol Cancer Ther, 2005, 4 (9): 1399-1408
2.Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry[J]. Circ Res, 2003, 92 (8): 827-839
3.Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression [J]. Nat Rev Cancer, 2002, 2 (3):161-174
4.Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior[J]. Annu Rev Cell Dev Biol, 2001, 17: 463-516
5.Nagase H. Activation mechanisms of matrix metalloproteinases[J]. Biol Chem, 1997, 378 (3-4):151-160
6.Baker AH, Edwards DR, Murphy G. Metalloproteinase inhibitors: biological actions and therapeutic opportunities[J]. J Cell Sci, 2002, 115 (Pt 19): 3719-3727
7.Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function[J]. Biochim Biophys Acta, 2000, 1477 (1-2): 267-283
8.Nawrocki B, Polette M, Marchand V, et al. Expression of matrix metalloproteinases and their inhibitors in human bronchopulmonary carcinomas: quantificative and morphological analyses[J]. Int J Cancer, 1997, 72 (4): 556-564
9.Drac P, Klein J, Tichy T, et al. Prognostic impact of matrix metalloproteinases 2, 9, and 11 in stromal cells stage I non-small cell lung cancer[J]. Cas Lek Cesk, 2007, 146 (1): 45-47
10.Ishikawa S, Takenaka K, Yanagihara K, et al. Matrix metalloproteinase-2 status in stromal fibroblasts, not in tumor cells, is a significant prognostic factor in non-small-cell lung cancer[J]. Clin Cancer Res, 2004, 10 (19): 6579-6585
11.Kim SH, Choi HY, Lee J, et al. Elevated activities of MMP-2 in the non-tumorous lung tissues of curatively resected stage I NSCLC patients are associated with tumor recurrence and a poor survival[J]. J Surg Oncol, 2007, 95 (4): 337-346
12.Gill JH, Kirwan IG, Seargent JM, et al. MMP-10 is overexpressed, proteolytically active, and a potential target for therapeutic intervention in human lung carcinomas[J]. Neoplasia, 2004, 6 (6): 777-785
13.Galateau-Salle FB, Luna RE, Horiba K, et al. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in bronchial squamous preinvasive lesions[J]. Hum Patho1, 2000, 31 (3): 296-305
14.Thomas P, Khokha R, Shepherd FA, et al. Differential expression of matrix metallo- proteinases and their inhibitors in non-small cell lung cancer[J]. J Pathol, 2000, 190 (2): 150-156
15.Simi L, Andreani M, Davini F, et al. Simultaneous measurement of MMP9 and TIMP1 mRNA in human non small cell lung cancers by multiplex real time RT-PCR[J]. Lung Cancer, 2004, 45 (2): 171-179
16.Gouyer V, Conti M, Devos P. Tissue inhibitor of metalloproteinase 1 is an independent predictor of prognosis in patients with non-small cell lung carcinoma who undergo resection with curative intent[J]. Cancer, 2005, 103 (8): 1676-1684
17.Suzuki M, Iizasa T, Fujisawa T, et al. Expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases in non-small-cell lung cancer[J]. Invasion Metastasis, 1998-1999, 18 (3): 134-141
18.Pritchard SC, Nicolson MC, Lloret C, et al. Expression of matrix metallo- proteinases 1, 2, 9 and their tissue inhibitors in stage II non-small cell lung cancer: implications for MMP inhibition therapy[J]. Oncol Rep, 2001, 8 (2): 421-424
19.Cox G, Jones JL, Andi A, et al. A biological staging model for operable non-small cell lung cancer[J]. Thorax, 2001, 56 (7): 561-566
20.Delebecq TJ, Porte H, Zerimech F, et al. Overexpression level of stromelysin 3 is related to the lymph node involvement in non-small cell lung cancer[J]. Clin Cancer Res, 2000, 6 (3): 1086-1092
21.Kren L, Goncharuk VN, Krenova Z, et al. Expression of matrix metalloproteinases 3, 10 and 11 (stromelysins 1, 2 and 3) and matrix metalloproteinase 7 (matrilysin) by cancer cells in non-small cell lung neoplasms. Clinicopathologic studies[J]. Cesk Patol, 2006, 42 (1): 16-19
22.Sasaki H, Yukiue H, Moiriyama S, et al. Clinical significance of matrix metalloproteinase-7 and Ets-1 gene expression in patients with lung cancer[J]. J Surg Res, 2001, 101 (2): 242-247
23.Byun JH, Lee MA, Roh SY, et al. Association between cyclooxygenase-2 and matrix metalloproteinase-2 expression in non-small cell lung cancer[J]. Jpn J Clin Oncol, 2006, 36 (5): 263-268
24.Yamamura T, Nakanishi K, Hiroi S, et al. Expression of membrane- type-1- matrix metallo- proteinase and metalloproteinase-2 in nonsmall cell lung carcinomas[J]. Lung Cancer, 2002, 35 (3): 249-255
25.Pinto CA, Carvalho PE, Antonangelo L, et al. Morphometric evaluation of tumor matrix metaloproteinase 9 predicts survival after surgical resection of adeno-carcinoma of the lung[J]. Clin Cancer Res, 2003, 9 (8): 3098-3104
26.Leinonen T, Pirinen R, Bohm J, et al. Expression of matrix metalloproteinases 7 and 9 in non-small cell lung cancer. Relation to clinicopathological factors, beta-catenin and prognosis[J]. Lung Cancer, 2006, 51 (3): 313-321
27.Hofmann HS, Bartling B, Simm A, et al. Identification and classification of differentially expressed genes in non-small cell lung cancer by expression profiling on a global human
59.620-element oligonucleotide array[J]. Oncol Rep, 2006, 16 (3): 587-595
28.Aljada IS, Ramnath N, Donohue K, et al. Upregulation of the tissue inhibitor of metallo- proteinase-1 protein is associated with progression of human non-small cell lung cancer[J]. J Clin Oncol, 2004, 22 (16): 3218-3229
29.Mino N, Takenaka K, Sonobe M, et al. Expression of tissue inhibitor of metalloproteinase-3 (TIMP-3) and its prognostic significance in resected non-small cell lung cancer[J]. J Surg Oncol, 2007, 95 (3): 250-257
30.Herbst RS, Yano S, Kuniyasu H, et al. Differential expression of E-cadherin and type IV collagenase genes predicts outcome in patients with stage I non-small cell lung carcinoma[J]. Clin Cancer Res, 2000, 6 (3): 790-797
31.Fujise N, Nanashim A, Taniguchi Y, et al. Prognostic impact of cathepsin B and matrix metalloproteinase-9 in pulmonary adenocarcinomas by immunohistochemical study[J]. Lung Cancer, 2000, 27 (1): 19-26
32.Yamaguchi NH, Lichtenfels AJ, Demarchi LM, et al. COX-2, MMP-9, and Noguchi classification provide additional prognostic information about adenocarcinoma of the lung. A study of 117 patients from Brazil[J]. Am J Clin Pathol, 2004, 121 (1): 78-86
33.Swinson DE, Cox G, O' Byrne KJ, et al. Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non- small-cell lung cancer[J]. Br J Cancer, 2004, 91 (7): 1301-1307
34.王静, 苗丽君, 吴逸明, 等. 非小细胞肺癌组织中AKT2、Cyclin D1、MMP-9表达及其 与临床病理因素的关系[J]. 癌症, 2006, 25 (1): 69-72
35.Ferrigan L, Wallace WA. Predicting non-small cell lung cancer expression of epidermal growth factor receptor and matrix metalloproteinase 9 from immunohistochemical staining of diagnostic biopsy samples[J]. Eur J Cancer, 2004, 40 (10): 1589-1592
36.Mari BP, Anderson IC, Mari SE, et al. Stromelysin-3 is induced in tumor/stroma coculturesand inactivated via a tumor-specific and basic fibroblast growth factor-dependent mechanism[J]. J Biol Chem, 1998, 273 (1): 618-626
37.Gonzalez-Avila G, Iturria C, Vadillo F, et al. 72-kD (MMP-2) and 92-kD (MMP-9) type IV collagenase production and activity in different histologic types of lung cancer cells[J]. Pathobiology, 1998, 66 (1): 5-16
38.Lizasa T, Fujisawa T, Suzuki M, et al. Elevated levels of circulating plasma matrix metallo- proteinase 9 in non-small cell lung cancer patients[J]. Clin Cancer Res, 1999, 5(1):149-153
39.Ylisirnio S, Hoyhtya M, Turpeenniemi-Hujanen T. Serum MMP-2, -9 and TIMP-1, -2 in lung cancer-TIMP-1 as a prognostic marker[J]. Anticancer Res, 2000, 20 (2B): 1311-1316
40.Laack E, Kohler A, Kugler C, et al. Pretreatment serum levels of matrix metalloproteinase-9 and vascular endothelial growth factor in non-small-cell lung cancer[J]. Ann Oncol, 2002, 13 (10): 1550-1557
41.Bugdayci G, Kaplan T, Sezer S, et al. Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer[J]. Exp Oncol, 2006, 28 (2): 169-171
42.Hrabec E, Strek M, Nowak D, et al. Elevated level of circulating matrix metalloproteinase-9 in patients with lung cancer[J]. Respir Med, 2001, 95 (1): 1-4
43.Susskind H, Hymowitz MH, Lau YH, et al. Increased plasma levels of matrix metallo- proteinase-9 and tissue inhibitor of metalloproteinase-1 in lung and breast cancer are altered during chest radiotherapy[J]. Int J Radiat Oncol Biol Phys, 2003, 56 (4): 1161-1169
44.Koc M, Ediger D, Budak F, et al. Matrix metalloproteinase-9 (MMP-9) elevated in serum but not in bronchial lavage fluid in patients with lung cancer[J]. Tumori, 2006, 92 (2): 149-154
45.Tamura M, Oda M, Matsumoto I, et al. The combination assay with circulating vascular endothelial growth factor (VEGF)-C, matrix metalloproteinase-9, and VEGF for diagnosing lymph node metastasis in patients with non-small cell lung cancer[J]. Ann Surg Oncol, 2004, 11 (10): 928-933
46.Laack E, Scheffler A, Burkholder I, et al. Pretreatment vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) serum levels in patients with metastatic non-small cell lung cancer (NSCLC)[J]. Lung Cancer, 2005, 50 (1): 51-58
47.赵军, 刘叙仪, 张青, 等. 晚期非小细胞肺癌患者外周血 VEGF 和 bFGF 及 MMP-9 水平与预后的关系[J]. 中华肿瘤杂志, 2005, 27 (11): 676-679
48.Yang SF, Hsieh YS, Lin CL, et al. Increased plasma levels of urokinase plasminogen activator and matrix metalloproteinase-9 in nonsmall cell lung cancer patients[J]. Clin ChimActa, 2005, 354 (1-2): 91-99
49.Eickelberg O, Sommerfeld CO, Wyser C, et al. MMP and TIMP expression pattern in pleural effusions of different origins[J]. Am J Respir Crit Care Med, 1997, 156 (6): 1987-1992
50. Di Carlo A, Terracciano D, Mariano A, et al. Matrix metalloproteinase-2 and matrix metalloproteinase-9 type IV collagenases in serum of patients with pleural effusions[J]. Int J Oncol, 2005, 26 (5): 1363-1368
51.Jin HY, Lee KS, Jin SM, et al. Vascular endothelial growth factor correlates with matrix metalloproteinase-9 in the pleural effusion[J]. Respir Med, 2004, 98 (2): 115-122
52.Reichenberger F, Eickelberg O, Wyser C, et al . Distinct endobronchial expression of matrix metalloproteinases (MMP) and their endogenous inhibitors in lung cancer[J]. Swiss Med Wkly, 2001, 131 (19-20): 273-279
53.Hakoda Y, Ito Y, Nagate A, et al. Increased collagenase activity in macrophages from brochial lavage as a diagnostic marker of non-small cell lung cancer[J]. Thorax, 2003, 58 (2): 122-126
54.Moses MA, Wiederschain D, Loughlin KR, et al. Increased incidence of matrix metallo- proteinases in urine of cancer patients[J]. Cancer Res, 1998, 58 (7): 1359-1399
55.Durkan GC, Nutt JE, Rajjayabun PH, et al. Prognostic significance of matrix metallo- proteinase-1 and tissue inhibitor of metalloproteinase-1 in voided urine samples from patients with transitional cell carcinoma of the bladder[J]. Clin Cancer Res, 2001, 7 (11): 3450-3456
56.Giavazzi R, Taraboletti G. Preclinical development of metalloproteasis inhibitors in cancer therapy[J]. Crit Rev Oncol Hematol, 2001, 37 (1): 53-60
57.Shinoda K, ShibuyaM, Hibino S, et al. A novel matrix metalloproteinase inhibitor, FYK 21388 suppresses tumor growth, metastasis and angiogenesis by human fibrosarcoma cell line[J]. Int J Oncol, 2003, 22 (2): 281-288
58.Fujino H, Kondo K, Ishikura H, et al. Matrix metalloproteinase inhibitor MMI-166 inhibits lymphogenous metastasis in an orthotopically implanted model of lung cancer[J]. Mol Cancer Ther, 2005, 4 (9): 1409-1416
59.Santos MA, Enyedy EA, Nuti E, et al. Methotrexate gamma-hydroxamate derivatives as potential dual target antitumor drugs[J]. Bioorg Med Chem, 2007, 15 (3): 1266-1274
60.Shepherd FA, Giaccone G, Seymour L, et al. Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to first-line chemo-therapy in patientswith small-cell lung cancer: a trial of the National Cancer Institute of Canada -Clinical Trials Group and the European Organization for Research and Treatment of Cancer[J]. J Clin Oncol, 2002, 20 (22): 4434-4439
61.Douillard JY, Peschel C, Shepherd F, et al. Randomized phase II feasibility study of combining the matrix metalloproteinase inhibitor BMS-275291 with paclitaxel plus carbo- platin in advanced non-small cell lung cancer[J]. Lung Cancer, 2004, 46 (3): 361-368
62.Itoh T, Tanioka M, Yoshida H, et al. Reduced angiogenesis and tumor progression in gelatinase A-deficient mice[J]. Cancer Res, 1998, 58 (5): 1048-1051
63.Li H, Lindenmeyer F, Grenet C, et al. Ad TIMP-2 inhibits tumor growth, angiogenesis, and metastasis, and prolongs survival in mice[J]. Hum Gene Ther, 2001, 12 (5): 515-526
64.孙建新, 张从昕, 殷学平, 等. 重组金属蛋白酶抑制因子-3 抗肿瘤作用的实验研究[J]. 中华肿瘤杂志, 1998, 20 (4): 10-12
65.Park HI, Ni J, Gerkema FE, et al. Identification and characterization of human endometase (Matrix metalloproteinase-26) from endometrial tumor[J]. J Biol Chem, 2000, 275 (27): 20540-20544
66.Uria JA, Lopez-Otin C. Matrilysin-2, a new matrix metalloproteinase expressed in human tumors and showing the minimal domain organization required for secretion, latency, and activity[J]. Cancer Res, 2000, 60 (17): 4745-4751
67.de Coignac AB, Elson G, Delneste Y, et al. Cloning of MMP-26. A novel matrilysin-like proteinase[J]. Eur J Biochem, 2000, 267 (11): 3323-3329
68.Mattei MG, Roeckel N, Olsen BR, et al. Genes of the membrane-type matrix metallo- proteinase (MT-MMP) gene family, MMP14, MMP15, and MMP16, localize to human chromosomes 14, 16, and 8, respectively[J]. Genomics, 1997, 40 (1): 168-169
69.Marchenko GN, Ratnikov BI, Rozanov DV, et al. Characterization of matrix metallo- proteinase-26, a novel metalloproteinase widely expressed in cancer cells of epithelial origin[J]. Biochem J, 2001, 356 (Pt 3): 705-718
70.Marchenko ND, Marchenko GN, Strongin AY. Unconventional activation mechanisms of MMP-26, a human matrix metalloproteinase with a unique PHCGXXD cysteine-switch motif[J]. J Biol Chem, 2002, 277 (21): 18967-18972
71.Park HI, Turk BE, Gerkema FE, et al. Peptide substrate specificities and protein cleavage sites of human endometase/ matrilysin-2/ matrix metalloproteinase-26[J]. J Biol Chem, 2002, 277 (38): 35168-35175
72.Park HI, Jin Y, Hurst DR, et al. The intermediate S1' pocket of the endometase/matrilysin-2active site revealed by enzyme inhibition kinetic studies, protein sequence analyses, and homology modeling[J]. J Biol Chem, 2003, 278 (51): 51646-51653
73.Lee S, Park HI, Sang QX. Calcium regulates tertiary structure and enzymatic activity of human endometase/matrilysin-2 and its role in promoting human breast cancer cell invasion[J]. Biochem J, 2006 Dec 18
74.Marchenko GN, Marchenko ND, Leng J, et al. Promoter characterization of the novel human matrix metalloproteinase-26 gene: regulation by the T-cell factor-4 implies specific expression of the gene in cancer cells of epithelial origin[J]. Biochem J, 2002, 363 (Pt 2): 253-262
75.Marchenko ND, Marchenko GN, Weinreb RN, et al. Beta-catenin regulates the gene of MMP-26, a novel metalloproteinase expressed both in carcinomas and normal epithelial cells[J]. Int J Biochem Cell Biol, 2004, 36 (5): 942-956
76.Shaulian E, Karin M. AP-1 as a regulator of cell life and death[J].Nat Cell Biol, 2002, 4 (5): 131-136
77.Pilka R, Whatling C, Domanski H, et al. Epithelial expression of matrix metallo- proteinase-26 is elevated at mid-cycle in the human endometrium[J]. Mol Hum Reprod, 2003, 9 (5): 271-277
78.Li W, Savinov AY, Rozanov DV, et al. Matrix metalloproteinase-26 is associated with estrogen-dependent malignancies and targets alpha1-antitrypsin serpin[J]. Cancer Res, 2004, 64 (23): 8657-8665
79.Pilka R, Norata GD, Domanski H, et al. Matrix metalloproteinase-26 (matrilysin-2) expression is high in endometrial hyperplasia and decreases with loss of histological differentiation in endometrial cancer[J]. Gynecol Oncol, 2004, 94 (3): 661-670
80.Pilka R, Domanski H, Hansson S, et al. Endometrial TIMP-4 mRNA is high at midcycle and in hyperplasia, but down-regulated in malignant tumours. Coordinated expression with MMP-26[J]. Mol Hum Reprod, 2004, 10 (9): 641-650
81. Pilka R, Kudela M, Eriksson P, et al. MMP-26 mRNA and estrogen receptor alpha co-expression in normal and pathological endometrium[J]. Ceska Gynekol, 2005, 70 (1): 56-62
82.关立华, 魏力, 张淑兰. MMP-26 和 TIMP-4 在人正常月经周期中的表达[J]. 现代妇产科进展, 2006, 15 (11): 826-829
83.Savinov AY, Remacle AG, Golubkov VS, et al. Matrix metalloproteinase 26 proteolysis of the NH2-terminal domain of the estrogen receptor beta correlates with the survival of breastcancer patients[J]. Cancer Res, 2006, 66 (5): 2716-2724
84.Liu YE, Wang M, Greene J, et al. Preparation and characterization of recombinant tissue inhibitor of metalloproteinase-4 (TIMP-4)[J]. J Biol Chem, 1997, 272 (33): 20479-20483
85.Zhang J, Cao YJ, Zhao YG, et al. Expression of matrix metalloproteinase-26 and tissue inhibitor of metalloproteinase-4 in human normal cytotrophoblast cells and a choriocarcinoma cell line,JEC-3[J]. Mol Hum Reprod, 2002, 8 (7): 659-666
86.Zhao YG, Xiao AZ, Park HI, et al. Endometase/matrilysin-2 in human breast ductal carcinoma in situ and its inhibition by tissue inhibitors of metalloproteinases-2 and -4: a putative role in the initiation of breast cancer invasion[J]. Cancer Res, 2004, 64 (2): 590-598
87.Bar-Or A, Nuttall RK, Duddy M, et al. Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis[J]. Brain, 2003, 126 (Pt 12): 2738-2749
88.Goffin F, Munaut C, Frankenne F, et al. Expression pattern of metalloproteinases and tissue inhibitors of matrix-metalloproteinases in cycling human endometrium[J]. Biol Reprod, 2003, 69 (3): 976-984
89.Chegini N, Rhoton-Vlasak A, Williams RS. Expression of matrix metalloproteinase-26 and tissue inhibitor of matrix metalloproteinase-3 and -4 in endometrium throughout the normal menstrual cycle and alteration in users of levonorgestrel implants who experience irregular uterine bleeding[J]. Fertil Steril, 2003, 80 (3): 564-570
90.Pilka R, Noskova V, Domanski H, et al. Endometrial TIMP-4 mRNA is expressed in the stroma, while TIMP-4 protein accumulates in the epithelium and is released to the uterine fluid[J]. Mol Hum Reprod, 2006, 12 (8): 497-503
91.Pilka R, Oborna I, Lichnovsky V, et al. Endometrial expression of the estrogen-sensitive genes MMP-26 and TIMP-4 is altered by a substitution protocol without down-regulation in IVF patients[J]. Hum Reprod, 2006, 21 (12): 3146-3156
92.Pilka R, Kudela M, Hansson S, et al. MMP-26 expression in endometrial explants treated with estradiol and progesterone[J]. Ceska Gynekol, 2004, 69 (6): 467-471
93.郭志荣, 柏素霞, 张踞, 等. 基质金属蛋白酶-26 在正常妇女和子宫内膜异位症患者子宫内膜中的时空变化[J]. 生殖与避孕, 2003, 23 (4): 195-199
94.Mencaglia L. Hysteroscopy and adenocarcinoma[J]. Obstet Gynecol Clin North Am, 1995, 22 (3): 573-579
95.关立华, 张淑兰. MMP-26 在正常子宫内膜和子宫内膜癌组织中的表达[J]. 中华肿瘤防治杂志, 2006, 13 (9): 651-655
96.Tunuguntla R, Ripley D, Sang QX, et al. Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinases TIMP-3 and -4 in benign endometrium and endometrial cancer[J]. Gynecol Oncol, 2003, 89 (3): 453-459
97.Isaka K, Nishi H, Nakai H, et al. Matrix metalloproteinase-26 is expressed in human endometrium but not in endometrial carcinoma[J]. Cancer, 2003, 97 (1): 79-89
98.Li Q, Wang H, Zhao Y, et al. Identification and specific expression of matrix metallo- proteinase-26 in rhesus monkey endometrium during early pregnancy[J]. Mol Hum Reprod, 2002, 8 (10): 934-940
99.Qiu W, Bai SX, Zhao MR, et al. Spatio-temporal expression of matrix metallo- proteinase-26 in human placental trophoblasts and fetal red cells during normal placentation[J]. Biol Reprod, 2005, 72 (4): 954-959
100.仇巍, 赵亮, 柏素霞, 等. MMP-26 在人正常胎盘滋养层细胞中的表达及激活素 A 对其表达的调节[J]. 生物化学与生物物理进展, 2005, 32 (1): 25-32
101.赵亮, 尚涛, 王雁玲, 等. 基质金属蛋白酶-26 在妊娠早期和中期原代细胞滋养细胞中的表达[J]. 中华妇产科杂志, 2004, 39 (2): 117-119
102.Rebecca LJ, Lois AS, Zhao YC, et al. Expression of activin receptors, follistatin and betaglycan by human endometrial stromal cells; consistent with a role for activins during decidualization[J]. Mol Hum Reprod, 2002, 8 (4): 363-374
103.吴晓秋, 李玉侠, 付雅媛, 等. 基质金属蛋白酶 MMP-26 能有效促进人绒毛膜上皮癌细胞 JEG-3 浸润能力[J]. 2006, 33 (6): 524-530
104.Ripley D, Tunuguntla R, Susi L, et al. Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinase-3 and -4 in normal ovary and ovarian carcinoma[J]. Int J Gynecol Cancer, 2006, 16 (5): 1794-1800
105.Zhao YG, Xiao AZ, Newcomer RG, et al. Activation of pro-gelatinase B by endometase/ matrilysin-2 promotes invasion of human prostate cancer cells[J]. J Biol Chem, 2003, 278 (17): 15056-15064
106.王阳, 李伟, 李一雷, 等. 乳腺良、恶性病变组织中MMP-26蛋白的表达及其与ER的关系[J]. 临床与实验病理学杂志, 2006, 22 (2): 182-185
107.Lee S, Desai KK, Iczkowski KA, et al. Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor[J]. Cell Res, 2006, 16 (9): 750-758
108.Impola U, Uitto VJ, Hietanen J, et al. Differential expression of matrilysin-1 (MMP-7), 92 kD gelatinase (MMP-9), and metalloelastase (MMP-12) in oral verrucous and squamouscell cancer[J]. J Pathol, 2004, 202 (1): 14-22
109.Yamamoto H, Vinitketkumnuen A, Adachi Y, et al. Association of matrilysin-2 (MMP-26) expression with tumor progression and activation of MMP-9 in esophageal squamous cell carcinoma[J]. Carcinogenesis, 2004, 25 (12): 2353-2360
110.Bister VO, Salmela MT, Karjalainen-Lindsberg ML, et al. Differential expression of three matrix metalloproteinases, MMP-19, MMP-26, and MMP-28, in normal and inflamed intestine and colon cancer[J]. Dig Dis Sci, 2004, 49 (4): 653-661
111.Bister V, Salmela MT, Heikkila P, et al. Matrilysins-1 and -2 (MMP-7 and -26) and metalloelastase (MMP-12), unlike MMP-19, are up-regulated in necrotizing enterocolitis[J]. J Pediatr Gastroenterol Nutr, 2005, 40 (1): 60-66
112.Bister V, Kolho KL, Karikoski R, et al. Metalloelastase (MMP-12) is upregulated in the gut of pediatric patients with potential celiac disease and in type 1 diabetes[J]. Scand J Gastroenterol, 2005, 40 (12): 1413-1422
113.Ahokas K, Skoog T, Suomela S, et al. Matrilysin-2 (matrix metalloproteinase-26) is upregulated in keratinocytes during wound repair and early skin carcinogenesis[J]. J Invest Dermatol, 2005, 124 (4): 849-856
114.Vogt PM, Lehnhardt M, Wagner D, et al. Growth factors and insulin-like growth factor binding proteins in acute wound fluid[J].Growth Horm IGF Res,1998, 8(Suppl B):107-109
115.Van Mater D, Kolligs FT, Dlugosz AA, et al. Transient activation of beta- catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice[J]. Genes Dev, 2003, 17 (10): 1219-1224
116. Skoog T, Ahokas K, Orsmark C, et al. MMP-21 is expressed by macrophages and fibroblasts in vivo and in culture[J]. Exp Dermatol, 2006, 15 (10): 775-783
117.Pirila E, Korpi JT, Korkiamaki T, et al. Collagenase-2 (MMP-8) and matrilysin-2 (MMP-26) expression in human wounds of different etiologies[J]. Wound Repair Regen, 2007, 15 (1): 47-57
118.Kuivanen T, Ahokas K, Virolainen S, et al. MMP-21 is upregulated at early stages of melanoma progression but disappears with more aggressive phenotype[J]. Virchows Arch, 2005, 447 (6): 954-960
119.Emingil G, Kuula H, Sorsa T, et al. Gingival crevicular fluid matrix metalloproteinase-25 and -26 levels in periodontal disease[J]. J Periodontol, 2006, 77 (4): 664-671
120.李慧云, 吴增常. 五种基质金属蛋白酶基因在乳头状甲状腺癌中的表达[J]. 中华内分泌代谢杂志, 2003, 19 (6): 449-451
121.Ferlay J, Bray F, Pisani P, et a1. GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide, version 2.0. IARC CancerBase No.5 Lyon: IARC Press, 2004
122.Olson TM, Hirohata S, Ye J, et al. Cloning of the human tissue inhibitor of metallo- proteinase-4 gene (TIMP-4) and localization of the TIMP-4 and TIMP-4 genes to human chromosome 3p25 and mouse chromosome 6, respectively[J]. Genomics, 1998, 51 (1): 148-151
123.Greene J, Wang M, Liu YE, et al. Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4[J]. J Biol Chem, 1996, 271 (48): 30375-30380
124.Mountain CF. Revisions in the international system for staging lung cancer[J]. Chest, 1997, 111 (6): 1710-1717
125.Tseng JE, Kemp BL, Khuri FR, et al. Loss of Fhit is frequent in stage I non-small cell lung cancer and in the lungs of chronic smokers[J]. Cancer Res, 1999, 59 (19): 4798-4803
126.Martini N, Flehinger BJ, Zaman MB, et al. Prospective study of 445 lung carcinomas with mediastinal lymph node metastases[J]. J Thorac Cardiovasc Surg, 1980, 80 (3): 390-399
127.Balbin M, Fueyo A, Tester AM, et al. Loss of collagenase-2 confers increased skin tumor susceptibility to male mice[J]. Nat Genet, 2003, 35 (3): 252-257
128.Polakis P. Wnt signaling and cancer[J]. Genes Dev, 2000, 14 (15): 1837-1851
129.Barker N, Clevers H. Catenins, Wnt signaling and cancer[J]. Bioessays, 2000, 22 (11): 961-965
130.Szabo E, Riffe ME, Steinberg SM, et al. Altered cJUN expression: an early event in human lung carcinogenesis[J]. Cancer Res, 1996, 56 (2): 305-315
131.Volm M, van Kaick G, Mattern J. Analysis of c-fos, c-jun, c-erbB1, c-erbB2 and c-myc in primary lung carcinomas and their lymph node metastases[J]. Clin Exp Metastasis, 1994, 12 (4): 329-334
132. Ramer R, Eichele K, Hinz B. Upregulation of tissue inhibitor of matrix metallo- proteinases-1 confers the anti-invasive action of cisplatin on human cancer cells[J]. Oncogene, 2007, Mar 19
133.Desmard M, Amara N, Lanone S, et al. Carbon monoxide reduces the expression and activity of matrix metalloproteinases 1 and 2 in alveolar epithelial cells[J]. Cell Mol Biol, 2005, 51 (4): 403-408
134.Hoshino Y, Mio T, Nagai S, et al. Fibrogenic and inflammatory cytokines modulate mRNA expressions of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-3 in type II pneumocytes[J]. Respiration, 2001, 68 (5): 509-516
135.Elbashir SM, Martinez J, Patkaniowska A, et al. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate[J]. EMBO J, 2001, 20 (23): 6877-6888
136.Schor SL, Schor AM, Winn B, et al. The use of three-dimensional collagen gels for the study of tumor cell invasion in vitro: experimental parameters influencing cell migration into the gel matrix[J]. Int J Cancer, 1982, 29 (1): 57-62
137.Fire A, Xu S, Montgomery M K, et al. Potent and specific genetic interference by double- stranded RNA in Caenorhabduis elegans[J]. Nature, 1998, 391 (6669): 806-811
138.Ramaswamy G, Slack FJ. SiRNA: A guide for RNA silencing[J]. Chem Biol, 2002, 9 (10): 1053-1055
139.Hannon GJ. RNA interference[J]. Nature, 2002, 418 (6894): 244-251
140.Yu JY, DeRuiter SL, Turner DL. RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells[J]. Proc Natl Acad Sci USA, 2002, 99 (9): 6047-60052
141.Yang D, Buchholz F, Huang Z, et al. Short RNA duplexes produced by hydrolysis with Escherichia coli RNase III mediate effective RNA interference in mammalian cells[J]. Proc Natl Acad Sci USA, 2002, 99 (15): 9942-9947
142.Sui G, Soohoo C, Afar EB, et al. A DNA vector-based RNAi technology to suppress gene expression in mammalian cells[J]. Proc Natl Acad Sci USA, 2002, 99 (8): 5515-5520
143.Castanotto D, Li H, Rossi JJ. Functional siRNA expression from transfected PCR products[J]. RNA, 2002, 8 (11): 1454-1460
144.Hannon GJ, Chubb A, Maroney PA, et al. Multiple cis-acting elements are required for RNA polymerase III transcription of the gene encoding H1 RNA, the RNA component of human RNase P[J]. J Biol Chem, 1991, 266 (34): 22796-22799
145.J萨姆布鲁克, D.W. 拉塞尔著. 黄培堂译. 分子克隆实验指南: 第 3 版[M]. 北京: 科学出版社, 2002, 1276-1305
146.Liotta LA. Tumor invasion and metastases--role of the extracellular matrix : Rhoads Memorial Award lecture[J]. Cancer Res, 1986, 46 (1): 1-7
147.Rao JS, Gondi C, Chetty C, et al. Inhibition of invasion, angiogenesis, tumor growth, and metastasis by adenovirus-mediated transfer of antisense uPAR and MMP-9 in non-small cell lung cancer cells[J]. Mol Cancer Ther, 2005, 4 (9): 1399-1408