摘要
目的:通过检测RECK和基质金属蛋白酶( MMP) 2、9及微血管密度(MVD)在恶性卵巢上皮性肿瘤中的表达,了解其在卵巢恶性上皮性肿瘤中表达的特点,探讨卵巢癌中RECK与MMP- 2、MMP- 9及MVD表达的相关性。方法:应用链霉亲和素-生物素-辣根过氧化物酶法(SP法)对36例恶性卵巢上皮性肿瘤组织, 34例良性卵巢上皮性肿瘤组织中RECK和MMP-2、MMP-9及MVD的表达情况进行检测。结果: RECK在恶性卵巢上皮性肿瘤中的表达较良性卵巢上皮性肿瘤及正常卵巢组织明显减少,卵巢恶性上皮性肿瘤中的RECK表达与卵巢癌的临床分期、组织学类型、组织学分级及年龄无关。且在卵巢上皮性肿瘤中RECK的表达与MMP-2、MMP-9及MVD呈显著负相关。结论:RECK在卵巢恶性上皮性肿瘤中表达明显减少,MMP-2、MMP-9的表达增加可能与RECK在卵巢恶性上皮性肿瘤中的表达量减少有关。
Background: Ovarian cancer is a common gynecological tumors, all ages have the incidence, but the histological tumor types will vary. Ovarian cancer is female genital mutilation common malignant tumor of the three. Over the past 20 years, due to the application of effective chemotherapy, the malignant ovarian germ cell tumor effect has been significantly improved, the mortality rate downregulated from 90 percent to 10 percent, but the treatment of malignant ovarian epithelial tumors has not been improved, 5 year survival rate hovering at 30%-40%,the first mortality rate was gynecologic malignancies.Epithelial ovarian malignant tumor has become a serious threat of the main tumor to women's lives and health. MMP is the endopeptidase collectively which can degradate the physical circumstances of extracellular matrixion of the basement membrane, and is the most closely related to tumor invasion and metastasis in the class of proteolytic enzymes, MMP-2 and MMP-9 mainly belong to gelatinase, function withⅣcollagen as substrate for type role, and often as non-activity forms exist, and in malignant tumors was increased expression and activation.
RECK (reversion inducing cysteine rich proteinwith Kazal motifs) is a newly identified tumor suppressor gene, it has a unique function that inhibit matrix metalloproteinase (matrix matalloproteinases, MMPs) expression and activity, is a kind of matrix metalloproteinase inhibitor. And the expression of RECK gene has closely relation with tumor invasion and metastasis, and angiogenesis, research shows that, RECK gene expression in liver, pancreatic cancer, breast cancer, lung cancer was negatively correlated with tumor invasion, and gene expression higher RECK Patients often are clearly better prognosis in patients with low expression levels.
Objective: This paper mainly discusses RECK, MMP-2, MMP-9 and MVD in epithelial ovarian tumors and their clinical significance.
Methods: Using immunohistochemical SP detected 13 cases of well-differentiated epithelial ovarian tumors, 23 cases -poorly differentiated epithelial ovarian tumors, 34 patients with ovarian benign organizations and 15 cases of normal epithelial ovarian tissue RECK, MMP-2,MMP-9 expression at the same time observe the different organizations of the microvascular density (MVD).
Results: (1) RECK protein expression are mainly located in the cell cytoplasm,yellow or deep yellow, RECK protein in normal and benign ovarian epithelial ovarian tumors has a large number of positive cells,the rates were 80.0%, 88.2%, and the different expression of RECK protein in both was not significant (P=0.3805), and RECK protein in ovarian cancer was significantly reduced, the positive rate was 36.1%, compare with normal ovary and a benign ovarian tumor the difference was significant (χ~2=14.1674, P=0.0008,χ~2=31.8681, P=0). RECK protein in well-differentiated and-poorly differentiated malignant epithelial ovarian tumor expression were 38.5%, 34.8%, there was no significant difference between them (χ~2=0.1851, P=0.9116).RECK protein expressed in the Phase I-II, Phase III-IV malignant epithelial ovarian tumors rates were 57.1%, 22.7%, the expression between the two has no significant difference (χ~2=4.5247, P=0.1041).RECK protein expression in epithelial ovarian cancer patients was unrelated to age (p>0.05).RECK protein expression in epithelial ovarian tumors was unrelated to the pathological type(p>0.05). (2)MMP-2 protein positive staining localization in cells was at the cytoplasm, in brown or yellow or deep yellow. The expression in the normal tissue and ovarian benign epithelial ovarian tumor was low, the expression rates were 33.3%, 23.5%,and the difference was not significant (P=0.7184), MMP-2 protein in malignant ovarian epithelial tumors has high Expression of 69.4%, compare with ovarian normal tissue and benign epithelial ovarian tumors ,there were significant differences (χ~2=6.1085, P=0.0455,χ~2=16.3100, P=0.0003).In ovarian cancer different grade of MMP-2 protein in-poorly differentiated malignant epithelial ovarian tumor is high differentiation of malignant epithelial ovarian tumor expression rate increase, respectively, 46.2%, 82.60%, the difference is significant (P=0.0366).In ovarian cancer the expression of MMP-2 protein in Phase I-II was higher than Phase III-IV in the different clinical stages, their rates were 42.9%, 86.4%, the difference was significant (P=0.0111). the expression of MMP-2 protein in epithelial ovarian cancer patients was unrelated to age (P>0.05). the expression of MMP-2 protein in epithelial ovarian cancer patients was unrelated to pathological type (P>0.05).(3)MMP-9 protein positive staining localization in cells was at the cytoplasm, in brown or yellow or deep yellow.The expression in the normal tissue and ovarian benign epithelial ovarian tumor was low ,the positive rates were 26.7%, 23.5%, the difference between them was not significant (P=0.9727),the expression of MMP-9 in malignant ovarian epithelial tumors was high the expression rates was 69.4%, Compared with ovarian normal tissue and benign epithelial ovarian tumors the differences were significant(χ~2=8.1931, P= 0.0166,χ~2= 15.46734 P=0.0004). The expression of MMP-9 protein in ovarian cancer different levels classification were inceased, 46.2%, 78.3%,the difference was significant(P=0.0478). In the different clinical stages of MMP-9 expression in ovarian cancer in Phase I-II, III-IV respectively rate were 42.9%, 81.8%, the difference between the two was significant (P=0.0183).MMP-9 expression in epithelial ovarian cancer patients was unrelated to age (P>0.05). MMP-9 expression in epithelial ovarian cancer patients was unrelated to pathological type (P>0.05) (4) The the department of microvascular intensive was in mesenchymal and epithelial ovarian junction.The microvessel density in the normal tissue and ovarian benign epithelial ovarian tumor were lower, respectively 12.0933±4.3146, 12.4058±3.5680, the two had no significant difference (P=0.7922), in malignant ovarian epithelial tumors with high expression 24.75±4.8093, and compared with ovarian normal tissue and benign epithelial ovarian tumors the difference were significant (t=8.8127, P=0, t=12.1386, P=0). In ovarian cancer of different levels classification the MVD expressed increased, respectively 20.3692±2.2888,27.2260±4.0237, the difference between the two was significant (P<0.05).In ovarian cancer in the different clinical stages the MVD expression in the Phase I-II, III-IV, were respectively 22.4714±4.3142,26.2±4.6221, the difference between the two was significant (P=0.0210).The expression of MVD in epithelial ovarian cancer patients was unrelated to age (P>0.05). The expression of MVD in epithelial ovarian cancer patients was unrelated to pathological type (P>0.05).(5) the expression of RECK, MMP-2, MMP-9 and MVD.The expression of RECK protein and MMP-2 was significantly negatively correlated (r =-0.5057). The expression of RECK protein and MMP-9 were significantly negatively correlated (r=-0.5725). The expression of MMP-2 and MMP-9 were significantly positive correlation. The expression of RECK positive rate and MVD was significantly negatively correlated (r =-0.383,P=0.021),The expression of MMP-2 positive rate and MVD was significantly positive correlation (r=0.454, P=0.005), The expression of MMP-9 positive rate and MVD was significantly positive correlation (r=0.449, P=0.006).
Conclusions: 1. In malignant epithelial ovarian tumor tissues RECK protein expression significantly decreased, suggesting that the expression of RECK gene in the tumor tissue was reduced, so that the invasion of ovarian cancer cells was increased. 2. The expression of MMP-2, MMP-9 protein in malignant epithelial ovarian tumor has a significant increase ,the expression was significantly increased with the texture histologic grade, clinical period. In the course of malignant epithelial ovarian tumor invasion and metastasis the two has played an important role. 3. Microvascular density (MVD) in malignant epithelial ovarian tumors was significantly increased. The expression of microvessel density (MVD) was significantly increased with the texture histologic grade, clinical stage. Note that certain factors in malignant epithelial ovarian tumors led to the microvascular density (MVD) increased, but the increase in microvascular density lead to the malignant tumor invasion and metastasis. 4.In malignant epithelial ovarian tumor tissues RECK protein expression significantly decreased, and the expression of MMP-2 protein, MMP-9 protein and microvascular density (MVD) was markedly increased. With the texture histologic grade, clinical stage ,The first three joint can be detected as a prediction of common epithelial ovarian tumors of the degree of malignancy and metastasis of important indicators. 5. With the improvement of clinical stages, RECK protein expression was significantly reduced, suggesting that RECK missing state epithelial ovarian tumor cell invasion was markedly improved, and likely to be ovarian cancer invasion and metastasis, and RECK, MMP-2 protein, MMP-9 protein and microvascular density (MVD) in a negative correlation between the expression of RECK.Research and treatment methods for new anticancer drug development provides a new way of thinking, for human epithelial ovarian tumors treatment provides a new target.
引文
1 丰有吉,沈铿等.《妇产科学》.北京:人民卫生出版社.2006: 330-342.
2 Van de Wiele C, Oltenfreiter R. Imaging Probes targeting matrix metalloproteinases[J].Cancer Biother Radiopharm,2006,21(5): 409-417.
3 Takallashi C,Sheng Z,Horan TP,et al.Regulation of matrixmetalloProteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK [J].Proc Natl Aced Sci USA,1998,95(22):13221-13226.
4 Weidner N, Folkman J ,,Pozza F, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma [ J ]. J Natl Cancer Inst, 1992, 84 (24) : 1875
5 Vasala K,Paakko P,Turpeenniemi-HujanenT. Matrix metalloproteinase-2 immunoreactive protein as a prognostic marker in bladder cancer[J]. Urology,2003,62(5):952-957.
6 吴小华,黎海莉,宋俊芬等.基质金属蛋白酶-2在卵巢上皮性肿瘤组织中的表达及意义[J].中华妇产科杂志, 2001,36 (10): 621-624.
7 黄晓园,吴明富,庄亮等.人卵巢癌组织中Rac21蛋白和基质金属蛋白酶-2的表达及临床意义.华中科技大学学报(医学版),2004,33(3):330-334.
8 Huang LU,Garrett AP,Bell DA,et al.Differential expression of matrix metalloproteinase-9 and tissue. Inhibitor of Metalloproteinase-1 protein and mRNA in epithelial ovarian tumors [J].Gynecology Oncol,2000,77 (3) : 369-376.
9 李道成,梁立治,邓高丕.MMP-9 在上皮性卵巢癌组织中的表达及临床意义.[J]实用癌症杂志,2008,(23)1:1-3.
10 Demeter A,Szirmai K,Olah J,et al.Elevated expression of matrix metalloproteinase-9 and fibronectin concentration in recurrent epithelial Ovarian cancer[J].Orv Hetil,2004,145 (31):1617-1624
11 Ozalp S,Tanir HM,Yalcin OT,et al.Prognostic value of matrix metalloproteinase-9 ( gelatinase-B) expression in epithelial ovarian tumors[J].Eur J Gynaecol Oncol,2003,24(5):417.
12 Lengyel E, Schmalfeldt B, Konik E. Exp ression of latent matrix metalloproteinase 9 (MMP-9) predicts survival in advanced ovarian cancer[J].Gynecol Oncol, 2001, 82 (2):291-298.
13 Murthi P,Barker G, Nowell CJ,et al.Plasminogen fragmentation and increased production of extracellular matrix-degrading proteinase are associated with serous epithelial ovarian progression [J].Gynecol Oncol,2004, 92(1):80-88.
14 Fang J,Shing Y,Wiedersehain D, et al. Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor mode[J].Pror Natl Acad Sci ,2000,97(8):3884-3889.
15 何爱保,罗永红,张轶清等.基质金属蛋白酶-2、血管内皮生长因子与卵巢上皮性肿瘤血管生成的关系[J].皖南医学院学报,2006, 25(2):101-104.
16 夏庆安,沈福海,吴瑜等.卵巢癌中γ-synuclein、MMP-9、MVD 的表达及意义.山东医药,2007,47(30):65-66.
17 Oshizaki T,Sato H.Furukawa M. Recent advances in the regulation of matrix metalloProteinase2 activation:from basic research to clinical implication (Review)[J].Oncol ReP,2002,9(3):607-611.
18 陈华江,王杰军.基质金属蛋白酶的结构及其调节机制[J].国外医学肿瘤分册,2001,28(l):21-23.
19 王长友,王伟.基质金属蛋白酶及其抑制物在膀胱癌中的相关性研究进展[J].肿瘤防治研究,2004,31(7):451-453.
20 Hofmann UB,Westphal J R,Van Kraats AA,et al.Expression of integrin alpha (v) beta (3) correlates with activation of membrane- type matrix Metalloproteinases-1(MT1-MMP) and metalloproteinases-2(MMP-2)in Human melanoma cells in vitro and in vivo[J].Int JCancer,2000,87(1):12-19.
21 Sternlicht MD,Werb Z.How matrix metalloproteinases regulate cell behavior.Annu Rev Cell Dev Biol,2007,17:463-516.
22 刘韬,马岩,张锐.基质金属蛋白酶与恶性肿瘤侵袭和转移关系的研究进展.吉林大学学报(医学版),2004,30(4):662-664.
23 Riedel F,Gotte K,Schwalb J,et al.Expression of 92-kDa type Ⅳ collagenase correlates with angiogenic markers andpoor survival in head and neck squamous cell carcinoma [J ].Int J Oncol,2000,17 (6):1099-1105.
24 Vuth,Shipley JM,Bergers G,et al.Gelatinases is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes[J].Cell, 1998,93(3):411-422.
25 乌肠喻,曾甫清.基质金属蛋白酶 9 与膀胱癌的研究进展[J].临床泌尿外科杂志,2004,19(9):572-575.
26 Sato H,Seiki M.Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells [J].Oncogene,1993,8(2):395-405.
27 冷启新,李瑞祥,刘执玉等.基质金属蛋白酶-9 的研究进展[J].四川解剖学杂志,2000(8)2:92-97.
28 Itoh T,Tanioka M,Matsuda H,et al.Experimental metastasis is suppressed in MMP-9-deficient mice.Clin Exp Metastasis,1999, 17 (2) :177.
29 Huang S,ArsdallMV,Tedjarati S,et al.Contributions of stromal metalloproteinase-9 to angiogenesis and growth in human ovarian carcinoma in mice[J]. J Natl Cancer Inst,2002,94(15):1134.
30 Powell WC,Knox JD,Navre M,et al.Expression of the metallop roteinase matrilysin in DU-145 cells increases their invasive potential in severe combined immunodeficient mice[J].Cancer Res,1993,53(2):417-422.
31 Mott JD,Werb Z.Regulation of matrix biology by matrix metalloproteinases.Curr Opin Cell Biol,2004,16(5):558-564.
32 Jodele S,Chantrain CF,Blavier L,et al.The contribution of bone marrow-derived cells to the tumor vasculature in neuroblastoma is matrix metalloproteinase-9 dependent.Cancer Ras,2005,65 (8) : 3200-3208.
33 Folkma J.Tumor angiogenesis:therapeutic implications.N Engl Med, 1971,285:1182-1186.
34 Risau W.Mechanisms of angiogenesis.Nature,1997,386 (6626): 671-674.
35 Orre M,Miri LM,Mamers P,et al.Increased mirrovessle density in mucinous compared with malignant serous and benign tumors of the ovary[J].Br J Cancer,1998,7(12):2204-2209.
36 Orre M,Rogers PA.Reduced vascular basement-membrane immunostaining in mucinous tumors of the ovary[J].Int,J cancer,1998, 79(2):139-143
37 Darai E,Bringuier AF,Walker CF,et al.CD31 expression in benign, borderline,and malignant epithelial ovarian tumors:An immunohistochemicaland serological analysis[J].Gynecol Oncol, 1998, 71(1):122-127.
38 RaspolliniMR,Amunni G,Villanucci A,et al.Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma[J].Int J Gynecol Cancer,2004,14 (5): 815 -823.
39 Hollingsworth HC,KOHA EC.STEINBERG SM,et al.Tumor angiogenesis in advanced stage ovarian carcinoma[J].AmJ Pathol, 1995,147(1):33-41.
40 Eisenberg I,Hochner H,Sadeh M ,et al.Establishment of the genomic structure and identification of thirteen single-nucleotide Polymorphisms in the human RECK gene[J].Cytogenet Genome Res,2002,97(l-2):58-61.
41 Pinto CA,Carvalho PE,Antonangelo L,et al.Morphometric evaluation of tumor matrix matalloProteinase9 predicts survival after surgical resection of adenocarcinoma of the lung[J].Clin Cancer Res,2003,9(8):3098-3104
42 Welm B,Mott J ,Werb Z.Developmental biology:vasculogenesis is awreck without RECK[J].Curr Biol,2002,12(6):R209-R211.
43 Takahashi C,Sheng Z,Horan TP,et al.Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK[J].Proc Natl Acad Sci USA,1998,95(22):13221-13226.
44 van der Japt MF,Sweep FC,Wass ET,et al.Correlation of reversion-indueing cysteine-rich protein with kazal motifs(RECK) and extracellular matrix Metalloproteinase inducer(EMMPRIN),with MMP-2,MMP-9,and survival in colorectal cancer[J].Cancer Lett,2006,237(2):259-297.
45 Masui T,Doi R,Koshiba T,et al.RECK expression in pancreatic cancer:its correlation with lower invasiveness and better Prognosis[J].Clin Cancer Res,2003,9(5):1779-1784.
46 杨德君,孟子辉,张纯海等.重组腺病毒介导既CK基因在大肠癌细胞中的表达及抑制癌细胞浸润能力的实验研究[J].中国实验诊断学,2005, 9(2): 192-194.
47 张勇,郑启昌,卢听等.肿瘤抑制基因 RECK 在胃癌中的表达及临床意义[J].肿瘤防治杂志,2005,12(2):110-113.
48 Furumoto K,Arii S,Mori A,et al.RECK gene expression in hepatocellular carcinoma:correlation with invasion-related clinicopathological factors and it clinical significance. Reverse-inducing- cystein-rich protein with Kazal motifs [J].HePatology,2001, 33(1):189-195.
49 Takenaka K,Ishikawa S,KawanoY,et al.Expression of a novel matrix metalloproteinase regulator,RECK,and its clinical significance in resected Non-smallcell lung cancer[J].Eur J Cancer,2004,40(10): 1617-1623.
50 徐振宇,高建平,张征宇等.RECK 基因在前列腺组织中的表达及其与基质金属蛋白酶的关系[J].医学研究生学报,2005,18(7): 577-598.
51 徐振宇,高建平,张征宇等.基质金属蛋白酶抑制剂 RECK 基因在前列腺细胞株中的表达及意义[J].中华男科学杂志,2005,11(10): 727-730.
52 李品,孙涛,魏雷震等.RECK 基因在脑胶质瘤细胞中的表达及其临床意义[J].中华神经外科杂志,2006,22(9):550-552.
53 Lei H, Hemminki K, Altieri A et al. Promoter polymorphisms in matrix metalloproteinases and their inhibitors: few associations with breast cancer susceptibility and progression.[J]Breast Cancer Res Treat. 2007,103(1): 61-69.
54 姚金光,李龙江,邝晓聪等.淋巴道转移舌鳞癌细胞 RECK、MMP-2、MMP-9 表达的动物实验研究[J].右江民族医学院学报,2006,25 (6):91l- 913.
55 张勇,郑启昌,卢听等.转染 RECK 基因对肝癌细胞生物学行为的影响[J]中国普外基础与临床杂志,2006,13(2):151-153.
56 Kondo S,Shukunami C,Morioka Y,et al.Dual effects of the membrane-anchored MMP regulator RECK on chondrogenic differentiation of ATDC5 cells. [J] Cell Sci. 2007,120(Pt 5):849-857.
57 Petruzzelli GJ,Benefield J,Yong S.Mechanism of lymph node metastases:current concepts[J].Otolaryngol Clin North Am,1998,31 (4):585-599.
58 Sasahara RM,Takahashi C,Noda M. Involvement of the SP1 site in ras-mediated down regulation of the RECK metastasis suppressor gene[J].Biochem BioPhys Res Commun,1999,264(3):668-675.
59 Mori T,Moriuchi R,Okazaki E,et al.Tgat oncoprotein functions as a inhibitor of RECK by association of the unique C-terminal region[J].Biochem Biophys Res Commun,2007,355(4):937-943.
60 Wood M,Fudge K,Mohler JL,et al.In situ hybridizationstudies of metalloproteinases 2 and 9 and TIMP-1 and TIMP-2 expression in human prostate cancer[J]Clin Exp Metastasis,1997,15 (3):246-258.
61 RM Takahashi C,Noda M. Involvement of the Sp1 site in ras-mediated downregulation of the RECK metastasis suppressor gene[J].BiochemBiophys Res Commun,1999,264(3):668-675.
62 Kang HG,Kim HS,Kim KJ et al.RECK expression in osteosarcoma: correlation with matrix metalloproteinases activation and tumor invasiveness[J].Orthop Res,2007,25(5):696-702.
63 Welm B,Mott J,Werb Z,Developmental biology:vasculogenesis is a wreck without RECK[J].Curr Biol,2002,12(6):R209-R211.
64 Oh J,Takahashi R,Kondo S,et al.The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis[J].Cell,2001,107(6):789-800.
65 Takenaka K,Ishikawa S,Kawano Y,et al.Expression of a novel matrix metalloproteinase regulator,RECK,and its clinical significance in resectednon-small cell lung cancer[J].Eur J Cancer,2004,40(10): 1617-1623.
1 Takahashi C, Sheng Z, Horan TP, Kitayama H,Maki M, Hitomi K, Kitaura Y, Takai S, Sasahara RM, Horimoto A, Ikawa Y, Ratzkin BJ, Arakawa T,Noda M. Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membraneanchored glycoprotein RECK. Proc Natl Acad Sci.USA 1998; 95: 13221-13226.
2 Eisenberg I,Hochner H,Sadeh M,et al.Establishment of the genomic structure and identification of thirteen single-nucleotide polymorphisms in the human RECK gene.Cytogenet Genome Res,2002,97(1-2):58-61.
3 Chang HC,Liu LT ,Hung WC. Involvement of histone deacetylation in ras-induced down-regultion of the metastasis suppressor RECK [J].Cell Signal,2004,16(6):675-679.
4 Sasahara RM , Takahashi C,Nda M.Involvement of the Sp1 site in ras-mediated downregulation of the RECK metastasis suppressor gene [J].Biochem BioPhys Res Commun,1999,264(3):668-675.
5 刘岩.肿瘤抑制基因 RECK 的功能及与肿瘤侵袭转移的关系 [J].生命的化学,2005,25(6):490-493.
6 李毅清,张勇,郑启昌等.RECK 基因真核表达载体的构建及在 HepG2 细胞中的表达.腹部外科,2005,18(5):314-317.
7 Verma RP.Hanseh C, et al. MatrixmetalloProteinases(MMPs): chmical-biological Fimctions and(Q)SARs[J].Bio org Med Chem ,2007,15(6): 2223-2268.
8 van der Japt MF,Sweep FC,Wass ET,et al.Correlation of reversion-inducing cysteine-rich protein with kazal motifs(RECK) and extracellular matrix Metalloproteinase inducer(EMMPRIN),with MMP-2,MMP-9,and survival in colorectal cancer [J]. Cancer Lett,2006,237(2):259-297.
9 张勇,郑启昌,卢听等.转染 REcK 基因对肝癌细胞生物学行为的影响[J].中国普外基础与临床杂志,2006,13(2):151-153.
10 Chang HC,Liu LT,Hung WC.Involvement of histone deacetylatio- nin ras-induced down-regulation of the metastasissuppressor RECK [J].Cell Signal,2004,16(6): 675-679.
11 Van Wart HE,Birkedal-Hansen H.The cysteine switch:a Principle of regulation of metalloproteinase activity with potential appliea- bility to the entire matrix metalloproteinase gene family[J].Proe Natl Aead Sci USA,1990,87(14):5578-5582.
12 Yoon SO,Park SJ,Yun CH,et al. Roles of matrie - Anchored MMP Inhibitor RECK Is a key regulator of extracellular matrix integrity and angiogenesis[J]. Cell,2001,107(6):789- 800.
13 徐振宇,高建平,孙颖浩.RECK 基因的研究进展[J].医学研究生学报,2005,18(4):361-368.
14 Oh J,Takallashi R,Kondo S,et al.The membrane-anehored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis [J].Cell,2001,107(6):789-800.
15 Rhee JS,Coussens LM.RECK and MMP function:implications for cancer development[J].Trends Cell Biol,2002,12(5):209-211.
16 Correa TC,Brohem CA,Winnisehofer SM,et al.Downregulation of the RECK tumor and metastasis suppressor gene in glioma invasiveness[J].Cell Biochem,2006,99(l):156-167.
17 Kang HG, Kim HS, Kim KJ et al. RECK expression in osteosarcoma: correlation with matrix metalloproteinases activation and tumor invasiveness[J]. Orthop Res. 2007, 25(5): 696-702.
18 J unseo Oh , Rei Takahashi,Shunya Kondo,et al.The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis [J].Cell,2001,107 (6):789-800.
19 Bryan Welm,Joni Mott,Zena Werb.Developmental biology: vasculogenesisis a wreck wit hout RECK [J].Curr Biol,2002,12 (6) : 209-211.
20 Welm B,Mott J,Werb Z. Developmental biology: vasculogenesis is a wreck without RECK [J].Curr Biol,2002,12(6):R209-R211.
21 Gomez DE, Aloneo DF, Yoshiji H, et al. Tissue inhibitors of metalloproteinase: structure,regulation and biological functions.[J] Eur J Cell Biol, 1997, 74(2): 111- 122.
22 Ishiguro K,Yamashita K,Nakagaki H,et al.Identification of tissue inhibitor of metalloproteinases-1(TIMP-1)in human teeth and its distribution in cementum and dentine.[J].Arch Oral Bid,1994,39 (4):345-349.
23 Bodden MK,Harber GI,Birkedal-Hansen B,et al.Functional domains of human TIMP-1(tissue inhibitor of metalloproreinases) [J] J Biol Chem,1994,269(29):18943-19852.
24 Noda M,OH J,Takahashi R,et al.RECK:a novel suppressor of malignancy linking oncogenic signaling to extracellular matrix remodeling[J].Cancer Metastasis Rev,2003,(3):167-175.
25 Oh J,Seo DW,Diaz T,et al.Tissue Inhibitors of Metalloproteinase 2 Inhibitors Endothelial Cell Migration through Increased Expression of RECK[J].Cancer Res,2004,64(24):9062-9069.
26 Oh J,Diaz T,Wei B,et al.TIMP-2 upregulates RECK expression via dephosphorylation of paxillin tyrosine residues 31 and 118[J]. Oncogene, 2006, 25(30):4230-4234.
27 Gontero P,Banisadr S,Frea B,et al.Metastasis markers in bladder cancer:a Review of the literature and clinical considerations[J].Eur Urol,2004,46 (3) :296-311.
28 Chang HC,Cho CY,Hung WC.Down regulation of RECK by Promoter Methylation correlates with lylnph node metastasis in non-small Cell lung cancer[J].Cancer Sci,2007,98(2):169-173.
29 Chang HC,Cho CY,Hung WC.Silencing of the metastasis suppressor RECK By RAS oncogene is mediated by DNA methyltransferase3b-inducedpromoter methylation[J].Cancer Res,2006,66(17):8413-8420.
30 Furumoto K, Arii S, Mori A, et al. RECK gene expression in hepatocellular carcinoma: correlation with invasion-related clinicopathological factors and its clinical significance [J]. Hepatology,2001, 33(1): 189-195.
31 汪多平,曹骥,赵荫农等.RECK及MMP-14在肝细胞肝癌组织中的表达及其临床意义.中国肿瘤临床,2007,34(10):558-562.
32 Masui T, Doi R, Koshiba T, et al. RECK expression in pancreatic cancer: its correlation with lower invasiveness and better prognosis[J]. Clin Cancer Res, 2003, 9(5): 1779-1784.
33 Van der Japt MF , Sweep FC , Wass ET,et al.Correlation of reversion-inducing cysteine-rieh protein with kazal motifs(RECK) and extracellular matrix metalloproteinase inducer(EMMPRIN),with MMP-2,MMP-9 , and survival in colorectal cancer[J].Cancer Lett ,2006,237(2):259-297.
34 杨德君,孟子辉,张纯海等.重组腺病毒介导既CK基因在大肠癌细胞中的表 达 及 抑 制 癌 细 胞 浸 润 能 力 的 实 验 研 究 [J]. 中 国 实 验 诊 断学,2005,9(2):192-194.
35 徐振宇,高建平,张征宇等.RECK 基因在前列腺组织中的表达及其与基质金属蛋白酶的关系[J].医学研究生学报,2005,18(7): 577-598.
36 徐振宇,高建平,张征宇等.基质金属蛋白酶抑制剂 RECK 基因在前列腺细胞株中的表达及意义[J].中华男科学杂志,2005,11(10): 727-730.
37 徐振宇,孙颖浩,高建平等.RECK基因在前列腺细胞株中的表达及其与MMP-2的关系. 江苏医药, 2007, 33(4): 372-374.
38 李喆,孙涛,魏雷震等.RECK 基因在脑胶质瘤细胞中的表达及其临床意义.中华神经外科杂志.2006,22(9):550-552.
39 Thomas GT,Lewis MP,Speight PM,et al. Matrix metalloproteinases and oral cancer[J]. Oral Oncol,1999,35(3):227-233.
40 Kumamoto H,Ooya K. Immunohistochemical detection of MT1 -MMP,RECK,and EMMPRIN in ameloblastic tumors [J]. J Oral Pathol Med,2006,35:345-351.
41 姚金龙,李龙江,邝晓聪等. RECK蛋白表达与舌鳞癌淋巴结转移和浸润的相关研究[J].广西医科大学学报,2006,23(4):536-537.
42 姚金龙,李龙江,邝晓聪等.淋巴道转移舌鳞癌细胞RECK、MMP -2和MMP-9表达的动物实验研究.右江民族医学院学报,2006,28(6):911-913.
43 李晟磊,赵志华,赵秋民等.食管鳞状细胞癌组织中 RECK 蛋白的表达与微血管密度检测.郑州大学学报(医学版),2007 ,42(6):1019-1022.
