Skp2、P27在口腔疣状癌中的表达研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:研究S期激酶相关蛋白Skp2与细胞周期素抑制因子p27在口腔疣状癌中的表达特点,探讨其与临床病理特点的关系,为口腔疣状癌的诊断、治疗及预后评估提供新的思路,为进一步了解口腔疣状癌与口腔鳞状细胞癌的区别和联系提供参考。
     方法:采用免疫组化SP法检测15例口腔疣状癌、30例口腔鳞癌和15例正常口腔粘膜标本中Skp2和p27蛋白的表达水平,SPSS12.0软件对数据进行统计学分析。
     结果:
     1.Skp2的表达Skp2在口腔疣状癌组、鳞癌组中的表达显著高于正常组(P<0.05),疣状癌和鳞癌组间比较无显著性差异(P>0.05)。疣状癌组中,按年龄、性别、肿瘤部位及临床分期等分组,Skp2的表达均无显著性差异(P>0.05);按临床分型分组,Skp2表达有显著差异(P<0.05)。鳞癌组中,按年龄、性别、肿瘤部位等分组,Skp2的表达均无显著性差异(P>0.05),按临床分期和恶性程度分组,临床分期越高、分化程度越低、有淋巴结转移者,Skp2表达越高,有显著性差异(P<0.05)。
     2.p27的表达p27在口腔疣状癌组、鳞癌组、和正常组三组的阳性表达率分别为43.3%,53.3%和93.3%,三组总体比较有显著性差异(P<0.05)。口腔疣状癌组、鳞癌组中的表达显著低于正常组(P<0.05),疣状癌和鳞癌组间比较无显著性差异(P>0.05)。疣状癌组中,按年龄、性别、肿瘤部位及临床分期等分组,p27的表达均无显著性差异(P>0.05);按临床分型分组,浸润/囊肿型p27表达显著低于外生型;鳞癌组中,按年龄、性别、肿瘤部位、临床分期等分组,p27的表达均无显著性差异(P>0.05),按恶性程度分组,分化程度越低、有淋巴结转移者,p27表达越低,差异有显著性(P<0.05)。
     3.Spearman等级相关分析表明,口腔疣状癌、口腔鳞癌组织中Skp2,p27表达均呈明显负相关(r_1=-0.935,P<0.05)、(r_2=-0.639,P<0.05)。
     结论:
     1.Skp2和p27可能参与了口腔疣状癌和口腔鳞癌的发生、发展过程,并与肿瘤的恶性程度密切相关。
     2.Skp2和p27可能在口腔疣状癌和口腔鳞癌的侵袭和转移过程中起起作用。
     3.Skp2可能是造成恶性肿瘤中p27表达下调的重要因素。
Objective:To study the expression of Skp2(S-Phase kinase associated Protein 2)and cyclin-dependent kinase inhibitor p27 in the oral verrucous carcinoma(OVC)and their relationship with clinicoPathologic characters,so as to provide a new way for early diagnosis,prognosis assessment and treatment of OVC.Besides,the results were compared with those of oral squamous cell carcinoma (OSCC)to discuss their difference and relationship.
     Methods:The immunohistochemistry technic was used to detect the expression of Skp2 and p27 in 15 OVC tissues,30 oral squamous carcinoma(OSCC)tissues and 15 normal oral mucosa tissues.Statistical analysis was performed by SPSS 12.0 software.
     Results:
     1.The expression of Skp2 The expression rates of Skp2 in the OVCs and OSCCs were significantly higher than those in normal mucosa (P<0.05),but there was no difference of Skp2 expression among the OVCs and OSCCs(P>0.05).In the OVCs,There was no difference of Skp2 expression in sex,age of the patients,as well as the tumour site or stage(P>0.05).For different phenotypes of OVC,the positive expression rate samples were different(P<0.05),while in the OSCCs,Skp2 expression was significantly associated with stages,differentiated grades and lymph node metastasis.The samples with higher stage,poorer differentiated grade or more probability lymph node metastasis had a significantly higher expression of Skp2.
     2.The expression of p27 The expression rates of p27 in the OVCs(43.5%)and OSCCs(53.3%)were significantly higher than those in normal mucosa(93.3%)(P<0.05).But there was no difference of p27 expression among the OVCs and OSCCs(P>0.05).In the OVCs,there was no difference of p27 expression in sex,age of the patients,tumour site,or stage(P>0.05).The positive expression rate samples of different types of OVC were different(P<0.05),while in the OSCCs,p27 expression was significantly associated with differentiated grades and lymph node metastasis,p27 staining in poorly differentiated carcinoma or more probability lymph node metastasis is remarkably reduced.
     3.Spearson anlysis showed that Skp2 was inversely associated with expression of p27 in OVC.(r_1=-0.935,P<0.01),and Skp2 was inversely associated with expression of p27 in OSCC.(r_2=-0.639,P<0.01)
     Conclusions:
     1.The expression of Skp2 and p27 may contribute to the carcinogenesis of OVC and OSCC,and has close relationship with the malignant potential of tumors.
     2.Skp2 and p27 may contribute to the progression and metastasis of OVC and OSCC.
     3.Skp2 plays an important role in the down-regulation of p27 during oral cancer development.
引文
[1]Ackerman LV.Verrucous carcinoma of the oral cavity.[J].Surgery.1948,(23):670-678
    [2]Koch BB.National survey of head and neck verrucous carcinoma.[J].Cancer.2001,(92):110-120
    [3]C.Kang,T.Chang,T.Chen,I,et al.104 oral cavity verrucous carcinoma.[J].European Journal of Cancer Supplements.2003,1,(5):536
    [4]Ferlito A,Rinaldo A,Mannara GM,et al.Is primary radiotherapy an appropriate option for the treatment of verrucous carcinoma of the head and neck.[J].Laryngol Otol 1998,112:132-139
    [5]Ferlito A,et al.Papillary squamous cell carcinoma versus verrucous squamous cell carcinoma of the head and neck.Ann Otol Rhinol Laryngol.1999,108:318-322
    [6]Kaugars GE et al.Oral verrucous carcinoma.[J].Oral SurgOral Med.1999,87:268-269
    [7]R.Depprich,J.Handschel,C.U.Fritzemeier,S.et al.Verrucous carcinoma of the oral cavity.[J].International Journal of Oral and Maxillofacial Surgery,2005,34(,1):138-140
    [8]N.Zwetyenga M E,Okeily,J.C.Fricain,C.et al.162 Oral verrucous carcinoma:Clinical data,natural history and results of treatment.[J].Oral Oncology Supplement,2005,1(1):196-199
    [9]TANG ZG,XIE XL,LI JY,et al.A clinic study on oral verrucous carcinoma phenotypes.[J].The Chinese Journal of Dental Research.2005,8(3):57-61
    [10]唐瞻贵,李晋芸,苏彤,等.口腔疣状癌的临床研究[J].口腔颌面外科杂志,2002,12(1):87-88
    [11]Miller CS,White DK.Human papillomavirus expression in oral mucosa,premalignant conditions and squamous cell carcinoma:a retrospective review.Oral Surg Oral Med Oral Pathol Oral Radiol Endo.1966,82:57-68
    [12]Kasperbauer JL,O'Halloran GI,Espy MJ,et al.Polymerase chain rection(PCR)identification of human papillomavirus(HPV)DNA in verrucous carcinoma of the larynx.Laryngoscope.1993,103:416-420
    [13]Bauer Hofmann R,Barghouts C,Auvinen E,et al.Genomic cloning and characterization of the nonoccupied allele correspounding to the integration site of human papillomavirus type 16 DNA in the cervical cancer cell lines SiHa.[J].Virology,1996,217:33-41
    [14]Badaracco G,Venuti A,Morello R,et al.Human papillomavirs in head and neck carcinomas:prevalence,physical status and relationship with clinical/pathological parameters.[J].Anticancer Res,2000,20(2):1301-1305
    [15]Shroyer KR,Greer RO,Fankhouser CA,et al.Detection of human papillomavirus DNA in oral verrucous carcinoma by polymerase chain reaction.[J].Mod Pathol,1993,6(6):669-72
    [16]Schepman KP,van der Meij EH,Smeele LE,et al.Malignant transformation of oral leukoplakia:a follow-up study of a hospital-based population of 166patients with oral leukoplakia from the Netherlands.[J].Oral Oncology 1998,34:270-275
    [17]Lopez-Amado M,Garcia-Caballero T,Lozano-Ramirez A,et al.Human papillomavirus and p53 oncoprotein in verrucous carcinoma of the larynx.[J].Laryngol Otol.1996,110:742-747
    [18]Gopalakrishnan R,Weghorst CM,Lehman TA.et al.Mutated and wild-type p53expression and HPV integration in proliferative leukoplakia and oral squamous cell carcinoma.[J].Oral Surgery,Oral Medicine,Oral Pathology,Oral Radiology,Endo-dontics 1997,83:471-478
    [19]GimenezConti IB,Collet AM,Lanfranchi H,et al.p53,Rb,and cyclin D1expression in human oral verrucous carcinomas.[J].Cancer.1996,78:17-23
    [20]Drachenberg CB,Blanchaert R,Ioffe OB,et al.Comparative study of invasive squamous cell carcinoma and verrucous carcinoma of the oral cavity,expression of bcl-2,p53,and Her-2/neu,and indices of cell turnover.[J].Cancer Detect Prev.1997,21:483-489
    [21]Punnya V,Angadi,Rekha Krishnapillai.et al.Cyclin D1 expression in oral squamous carcinoma and verrucous carcinoma:correlation with histological differentiation.[J].Oral Surgery,Oral Medicine,Oral Pathology,Oral Radiology,and Endodontology.2007,103(3):30-35
    [22]唐瞻贵,李晋芸,姚志刚,徐锡萍.口腔疣状癌E-cadherin基因蛋白免疫电镜研究.[J].口腔颌面外科杂志,2003,(04):95-97
    [23]唐瞻贵,邹萍,姚志刚,蒋海鹰,冯德云.MDM_2及p53在口腔疣状癌中的表达研究.[J].口腔颌面外科杂志,2004,(04):56-58
    [24]马康黎,唐瞻贵,刘友良,冯德云,姚志刚.口腔疣状癌中MMP-2的表达及意义.[J].临床口腔医学杂志,2004,(12):94-97
    [25]唐瞻贵,李金茂,洪珍珍,俞志维,刘程辉.基质金属蛋白酶2在口腔疣状癌和鳞癌中的表达.[J].中南大学学报(医学版),2005,(06):650-653
    [26]张雷,唐瞻贵,周正国,仝向娟,李晓玲.头颈部丝氨酸蛋白酶抑制剂基因、血管内皮生长因子在口腔疣状癌中的表达及意义.[J].口腔医学,2006,(02):97-100
    [27]Pietenpol JA,Bohlander SK,Sato Y,et al.Assignment of the human p27 kip1gene to 12p 13 and its analysis in leukemias.[J].Cancer Res,1995,55(6):1206
    [28]Polyak K,LeeMong Hong,Erdjument Bromage H,et al.Cloning of p27 Kip1,a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals.[J].Cell,1999,78(1)59-66.
    [29]Malek N P,Sundberg H,McGrew S,et al.A mouse knock-in model exposes sequential proteolytic pathways that regulate p27kip1 in G1 and S phase.[J].Nature.2001,413:326-328
    [30]Zhang H,Kobayashi R,Galaktionov K,et al.p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase.[J].Cell,1995,82(6):915-925
    [31]Schulman BA,Carrano AC,Jeffrey PD,et al.Insights into SCF ubiquitin ligases from the structure of the skp1-Skp2 complex.[J].Nature.2000,408(6810):381-386
    [32]Tsvetkov LM,Yeh KH,Lee SJ,et al.p27kip 1 ubiquitination and degradation is regulated by the SCFSkp2 complex through phosphoylated Thr 187 in p27.[J].Current Biology.1999,9(12):661-664
    [33]Carrano AC,Eytan E,Hershko A,et al.Skp2 is required for ubiquitin-Mediated degradation of the CDK inhibitor p27.[J].Nat Cell Boil,1999,1(4):193-199
    [34]Keiko Nakayama,Hiroyasu Nagahama,Yohji A,et al.Skp2-mediated degradation of p27 regulates progression into mitosis.[J].Developmental Cell,2004,5(6):661
    [35]Lin Douglas,Alan Diehl J.Mechanism of cell-cycle control:ligating the ligase [J].Trends in Biochemical Sciences,2004,29(9):453
    [36]Bloom J,Pagano M.Deregulated degradation of the cdk inhibitor p27 and malignant transformation.[J].Sem in Cancer Bio,2003,13(1):41-47
    [37]Kudo Y,Kitajima S,Sato S,et al.High expression of S-phase kinase interacting protein2,human F-box protein,correlates with poor prognosis in oral squamous cell carcinomas.[J].Cancer Res,2001,61(19):7044-7047
    [38] Takata T, Kudo, Zhao M,et al. Reduced expression of p27(Kip1) protein in relation to salivary adenoid cystic carcinoma metastasis.[J].Cancer. 1999, 86 (6):928-35
    [39] Gstaiger M, Jordan R, Lim M, et al. Skp2 is oncogenic and overexpressed in human cancers. [J] .Proceedings of the National Academy of Sciences of the United States of America. 2001, 98 (9):5043-5048
    [40] Masuda TA, Inoue H, Sonoda H, et al. Clinical and biological significance of S-phase kinase-associated protein2(Skp2)gene expression in gastric carcinoma: modulation of malignant phenotype by Skp2 overexpression, possibly via p27 proteolysis.[J].Cancer Res, 2002, 62 (13):3819-3825
    [41] Yokoi S, Yasui K, Saito Ohara F, et al. A novel target gene, Skp2, within the 5p13 amplicon that is frequently detected in small cell lung cancers.[J].Am J Pathol, 2002, 161 (1):207-216
    [42] Chiarle R, Fan Y, Piva R, et al. S-phase kinase-associated protein 2 expression in non-Hodgkin's lymphoma inversely correlates with p27 expression and defines cells in S phase.[J].Am J Pathol. 2002,160 (4):1457-1466
    [43] Oliveira AM, Okuno SH, Nascimento AG, et al. Skp2 protein expression in soft tissue sarcomas.[J].Clin Oncol. 2003,21, (4):722-727
    [44] Signoretti S D, Marcotullio L R, ichardson A, et al. Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer.[J]. Journal of Clinical Investigation, 2002,110 (5): 633 - 641
    [45] Masuda TA, Inoue H, Nishida K, et al. Cyclin-dependent kinase 1 gene expression is associated with poor prognosis in gastric carcinoma.[J].Clin Cancer Res. 2003, 9 (15):5693
    [46] OFER BI, SHIRLY LB, SHIMON M, et al. Inverse Relationship Between Skp2 Ubiquitin Ligase and the Cyclin Dependent Kinase Inhibitor p27Kip1 in Prostate Cancer. [J].The Journal of Urology. 2003,170 (1): 241-245
    [47] Yasusei Kudo, Shojiro Kitajima, etc. Down-regulation of Cdk inhibitor p27 in oral squamaous cell carcinoma.[J].Oral Oncology, 2005,41 (2):105-106
    
    [48] Fiano, Davide Schiffer, Paola Cavalla, Valentina. Inverse relationship between p27/Kip1 and the F-box protein Skp2 in human astrocytic gliomas by immunohistochemistry and Western blot.[J]. Neuroscience Letters Seminars in Cancer. 2002, 328, (2):125-128
    [49] Joanna Bloom, Michele Pagano. Deregulated degradation of the cdk inhibitor p27 and malignant transformation.[J].Biology,2003,13(1):41-47
    [50]Steven I.Reed.Skp'n with Cksl:Revelations from the Skp1-Skp2-Cks1-p27Structure.[J].Molecular Cell,2005,20(1):1-2
    [51]Zhang L,Wang C.F-box protein Skp2:a novel transcriptional target of EOF.[J].Oncogene,2006,25(18):2615-2627
    [52]Satoru Shintani,Churman Li,et al.Gefitinib(Iressa,ZD1839),an epidermal growth factor receptor tyrosine kinase inhibitor,up-regulates p27 and induces G1 arrest in oral squamous cell carcinoma cell lines,Oral Oncology,2004,40(1):43-51
    [53]Shintani S,Li C,Mihara M,et al.Skp2 and Jab1 expression are associated with inverse expression of p27(KIP1)and poor prognosis in oral squamous cell carcinomas.[J].Oncology.2003,65(4):355-362
    [54]Radier G,Makris C,Coulombe P,et al.P27 inhibits Glto S phase progression by down regulation expression of F-box protein Skp2.[J].Cell Bio,2005,168(1):55-66
    [55]Tsuzuki H,Fujieda S,Sunaga H,et al.Expression of p27 and apoptosis in oral leukoplakia.[J].Anticancer Res.2003,23(2B):1265
    [56]Mariko Mihara,Junya Yano,Nagaaki Terakado,et al.Gefitinib ("Iressa",ZD1839),an epidermal growth factor receptor tyrosine kinase inhibitor,up-regulate p27KIP and induces G1 arrest in oral squamous cell carcinoma cell line[J].2004,41(1):43-51
    [57]唐瞻贵,谢晓莉,粟红兵等.口腔粘膜疣状癌电镜观察机器与临床病理的联系.[J].湖南医科大学学报.1996,21(3):262-264
    [58]李晋芸,唐瞻贵,徐锡萍等.口腔疣状癌超微结构特征研究.[J].临床口腔医学杂志.2003,19(11):673-675
    [1]Pietenpol JA,Bohlander SK,Sato Y,et al.Assignment of the human p27 kip1 gene to 12p13 and its analysis in leukemias[J].Cancer Res,1995,55(6):1206
    [2]Bloom J,Pagano M.Deregulated degradation of the cdk inhibitor p27and malignant transformation[J].Sem in Cancer Biol,2003,13(1):41-47
    [3]Kawamata N,Morosetti R,Miller CW,et al.Molecular analysis of the cyclin-dependent kinase inhibitor gene p27/kip1 in human malignancies[J].Cancer Res,2995,55(11):2266-2269
    [4]Schulman BA,Carrano AC,Jeffrey PD,et al.Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex.[J].Nature,2003,408(6810):382-386
    [5]Lin Douglas,Alan Diehl J.Mechanism of cell-cycle control:ligating the ligase.[J].Trends in Biochemical Sciences,2004,29(9):453
    [6]Polyak K,LeeMong Hong,Erdjument Bromage H,et al.Cloning of p27Kip1,a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals . [J]. Cell, 1999, 78(1) 59- 66
    
    [7] Katayose Y, Kim M , Rakkar AN , et al. Promoting apoptosis : a novel activity associated with the cyclin2dependent kinase inhibitor p27.[J]. Cancer Res,1997, 57:5441-5445
    
    [8] Katner AL ,Hoang QB ,Gootam P ,et al. Induction of cell cycle arrest and apoptosis in human prostate carcinoma cells by a recombinant adenovirus expressing p27 (Kip1).[J]. Prostate, 2002, 53 (1):77-87
    [9] St Croix B, Florenes VA, Rak JW, et al. Impact of the cyclin-dependent kinase inhibitor p27Kip1 on resistance of tumor cells to anticancer agents.[J]. Nat Med, 1996,2(11):1204-1210
    [10] Zhang H, Kobayashi R, Galaktionov K, et al. p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase .[J]. Cell, 1995, 82(6):915-925
    [11] Demetrick DJ, Zhang H, Beach DH. Chromosomal mapping of the genes for the human CDK2/cyclin A-associated proteins p19 (SKP1A and SKP1B) and p45 (SKP2).[J]. Cytogenet Cell Genet, 1996, 73: 104-107
    [12] Tsvetkov LM, Yeh K-H, Lee S-J, et al. p27kip 1 ubiquitination and degradation is regulated by the SCFSkp2 complex through phosphoylated Thr 187 in p27.[J].Current Biology. 1999, 9 (12):661-664
    [13] MongayL, Plaza S, Vigorito E, et al. Association of the cell cycle regulatory proteins p45(SKP2) and CksHsl. Functional effect on CDK2 complexformation and kinase activity.[J]. Biol Chem, 2001, 276: 25030-25036
    [14] Kudo Y, Kitajima S, Ogawa I, et al. Down-regulation of CDK inhibitor p27 in oral squamous cell carcinoma.[J]. Oral Oncol, 2005, 41: 105-116
    [15] Carrano AC, Eytan E, Hershko A, et al. SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27.[J]. Nat Cell Biol, 1999, 1: 193-199
    [16] Lin DI, Diehl JA. Mechanism of cell-cycle control: ligating the ligase. Trends BiochemSci, 2004, 29: 453-455
    [17] Ezoe S, Matsumura I, Nakata S, et al. GATA22 Pestrogen receptor chimera regulates cytokine-dependent growth of hematopoietic cells through accumulation of p21 (WAF1) and p27 ( Kip1) proteins . [J]. Blood , 2002 ,100 (10):3512-3520
    [18] Carrano AC, Eytan E, Hershko A, et al. Skp2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27 .[J]. Nat Cell Boil, 1999, 1 (4): 193-199
    [19] Carrano AC,Eytan E,Hershko A,et al. Skp2 is required for ubiquitin-Mediated degradation of the CDK inhibitor p27.[J]. Nat Cell Boil, 1999,1 (4): 193-199
    [20] Bashir T, Dorrello NV, Amador V.etal. Control of the SCF(Skp2-Cks1) ubiquitin ligase by the APC/C(Cdhl) ubiquitin ligase.[J]. Nature 2004, 428:190-193
    [21] Keiko Nakayama,Hiroyasu Nagahama,Yohji A,et al. Skp2-mediated degradation of p27 regulates progression into mitosis. [J] .Developmental Cell, 2004, 5 (6):661
    [22] BaratzLS, lzhak BO, SaboE, etal. Decreased level of the cell cycle regulator p27 and increased level of its ubiquitin ligase Skp2 in endometrial carcinoma but not in normal secretory or in hyperstimulated endometrium.[J]. Mol Hum Reprort, 2004,10 (8):567-572
    [23] Zhang L, Wang C. F-box protein Skp2:a novel transcriptional target of E2F.[J]. Oncogene, 2006, 25 (18) :2615-2627
    [24] Masuda TA,Inouc H, Sonoda H , et al. Clinical and biological significance of S-phase kinase-associated protein 2 (Skp2) gene expression in gastric carcinoma : modulation of malignant phenotype by Skp2 overexpresssion, possibly via p27 proteolysis.[J].Cancer Res, 2002, 62 (13):3819-3825
    [25] Kazumori Kawakami, Hideki Enokida, Tokushi Tachiwada.et al. Increased Skp2 and CKS1 Gene Expression Contributes to the Progression of Human Urothelial Carcinoma.[J]. The Journal of Urology.2007,178(1):301-307
    [26] OFER BI, SHIRLY LB, SHIMON M, et al. Inverse Relationship Between Skp2 Ubiquitin Ligase and the Cyclin Dependent Kinase Inhibitor p27Kipl in Prostate Cancer.[J]. The Journal of Urology. 2003, 170 (1): 241-245
    [27] Kudo Y,Kitajima S,Sato S,et al. High expression of S-phase kinase interacting protein2 , human F-box protein,correlates with poor prognosis in oral squamous cell carcinomas.[J]. Cancer Res, 2001, 61 (19): 7044-7047
    [28] Zheng WQ, Zheng JM, Ma R, et al. Relationship between levels of Skp2 and p27 in breast carcinomas and possible role of Skp2 as targeted therapy.[J]. Steroids, 2005, 70(11):770-774
    [29] Yue H,Song FL,Znang N,et al. Expression of p27(kipl), Rb protein and proliferating cell nuclear antigen and its relationship with clinicopathology in haman pancreatic cancer. [J]. Hepatobiliary Pancreat Dis Int, 2003, 2 (1) :142-146
    [30] Radier G,Makris C,Coulombe P,et al. 107inhibits Glto S phase progression by downregulation expression of F-box protein Skp2[J] J Cell BioL, 2005, 168 (1):55-66
    [31] Dong Y, Sui L, Watanabe Y, et al. S-phase kinase-associated protein 2 expression in laryngeal squamous cell carcinomas and its prognostic implications .Oncology Reports, 2003,10(2):321-325
    [32] Slingerland J, Pagano M. Regulation of the CDK inhibitor p27 and its deregulation in cancer.[J]. Cell Physiol, 2000,183(1): 10-17
    [33] Fan GK, Xu FZ, Yang BB, et al. p57 (kip2) expression is related to carcinogenesis and tumor progression in laryngeal tissues .[J]. Acta Oto-laryngol. 2006, 126:301-305
    [34] Shigemasa K, Gu L, O 'Brien TJ, et al. Skp2 overexp ression is a prognostic factor in patients with ovarian adenocarcinoma.[J]. Clin Cancer Res. 2003, 9 (5):1756-1763
    [35] Ravaioli A, Monti F, Regan MM, etal. p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node negative early breast cancer. Ann Oncology.[J]. 2008,19 (4):660-668
    [36] Adriana Handra-Luca, Blandine Ruhin, Claude Lesty. et al. p27, Skp2, and extra-cellular signal-related kinase signalling in human salivary gland mucoepidermoid carcinoma.[J]. Oral Oncology. 2006, 42 (10): 1005-1010
    [37] Harada K, Supriatno, Yamamoto S, et al. Cepharanthine exerts antitumor activity on oral squamous cell carcinoma cell lines by induction of p27kip1.[J]. Anticancer Research, 2003,23 (9):1441-1448
    [38] Lin R, Wang TT, Miller WH, et al. Inhibition of f-box protein p45Skp2 expression and stabilization of cyclin-dependent kinase inhibitor p27kipl in vitamin Danalog treated cancer cells.[J]. Cancer Research, 2003, 144 (3):749-753
    [39] Wei qiang Zheng, Jian ming Zheng, Rong Ma. et al.Relationship between levels of Skp2 and p27 in breast carcinomas and possible role of Skp2 as targeted therapy.[J]. Steroids.2005, 70, (11): 770-774

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700