生长分化因子-9在人膀胱癌组织中的表达及其临床意义

符骏; 杜鹏; 杨勇

生长分化因子-9在人膀胱癌组织中的表达及其临床意义

- 1. 北京京煤集团总医院泌尿外科(北京, 102300);
- 2. 北京大学肿瘤医院暨北京市肿瘤防治研究所泌尿外科恶性肿瘤发病机制及转化研究教育部重点实验室(原单位:首都医科大学附属北京医院泌尿外科)
基金项目:
首都医科大学基础与临床合作基金（编号12JL41）

详细信息

通讯作者: 杜鹏,E-mail:dupeng9000@126.com

中图分类号: R737.14

收稿日期: 2013-01-12

Expression and its clinical significance of growth differentiation factor-9 in bladder cancer

- 1. Department of Urology, Beijing Jingmei Group General Hospital, Beijing, 102300, China;
- 2. Key laboratory of Carcinogenesis and Translational Research, Ministry of Education;Department of Urology, Peking University Cancer Hospital & Institute

More Information

Corresponding author: DU Peng, E-mail: dupeng9000@126.com

Received Date: 12 January 2013

摘要

摘要: 目的：探讨生长分化因子-9（growth differentiation factor-9， GDF-9）在人膀胱癌组织中的表达及其与膀胱癌病理分级和临床分期的关系。方法：运用免疫组化技术检测GDF-9在50例不同分期分级的膀胱癌组织和15例正常膀胱组织之间的蛋白表达情况。结果：①正常人膀胱组织中GDF-9呈高表达，且GDF-9蛋白主要定位于膀胱移行上皮细胞的胞浆中。而膀胱癌组织中GDF-9呈低表达或不表达。②GDF-9阳性表达率在膀胱癌病理分级间分别：Ⅰ级47.6%（10/21），Ⅱ级26.7%（4/15），Ⅲ级7.1%（1/14），差异具有统计学意义（P<0.05）。GDF-9阳性表达率在膀胱癌临床分期间分别：T_a~T₁期40.6%（13/32），T₂~T₃期11.1%（2/18），差异具有统计学意义（P<0.05）。结论：GDF-9在膀胱癌组织中低表达或不表达，且与膀胱癌病理分级和临床分期呈负相关。GDF-9可能是一个潜在的人膀胱肿瘤抑癌基因。
- 膀胱肿瘤 /
- 生长分化因子-9
Abstract: Objective: To investigate the expression of growth differentiation factor-9 (GDF-9) in bladder transitional cell carcinoma (BTCC) and its clinical significance in the malignancy of BTCC.Method: Immunohistochemical methods was used to detect GDF-9 protein in 50 cases of BTCC and 15 cases of normal bladder muscosa served as the controls.Result: In normal bladder tissues, stronger staining of GDF-9 was seen in transitional cells, both in the cytoplasm and in the nucleus. In contrast, the staining of GDF-9 was notably weak or absent in cancer cells of tumour tissues. The positive expression rate of GDF-9 in GradeⅠ, Ⅱ and Ⅲ according to pathological grade of BTCC was 47.6% (10/21), 26.7% (4/15) and 7.1% (1/14), respectively. There were significant differences among the three pathological grades. The positive expression rate of GDF-9 in Stage T_a-T₁ and T₂-T₃ according to clinical stages of BTCC was 40.6% (13/32) and 11.1% (2/18), respectively. There were significant differences between the two clinical stages.Conclusion: GDF-9 is expressed at lower levels in human bladder cancer tissues compared with normal transitional cells of the bladder. GDF-9 levels are inversely correlated with the pathological grade and clinical stages of bladder cancer. It suggests that GDF-9 is a potential tumour suppressor in human bladder cancer.
- bladder cancer /
- growth differentiation factor-9

HTML全文

参考文献(23)

[1]	张思维, 马建辉, 李鸣, 等. 中国部分市县膀胱癌发病趋势比较研究[J]. 中华泌尿外科杂志, 2009, 30(10):673-676.
[2]	Ploeg M, Aben K K, Kiemeney L A.The present and future burden of urinary bladder cancer in the world[J]. World J Urol, 2009, 27:289-293.
[3]	Aaltonen J, Laitinen M P, Vuojolainen K, et al. Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis[J]. J Clin Endocrinol Metab,1999, 84:2744-2750.
[4]	Bokobza S M, Ye L, Kynaston H, et al. Growth and differentiation factor 9 (GDF-9) induces epithelial-mesenchymal transition in prostate cancer cells[J]. Mol Cell Biochem, 2010, 349:33-40.
[5]	Hanavadi S, Martin T A, Watkins G, et al. The role of growth differentiation factor-9 (GDF-9) and its analog, GDF-9b/BMP-15, in human breast cancer[J]. Ann Surg Oncol, 2007, 14:2159-2166.
[6]	Zhuang Z, Jian P, Longjiang L, et al. Oral cancer cells with different potential of lymphatic metastasis displayed distinct biologic behaviors and gene expression profiles[J]. J Oral Pathol Med, 2009, 39:168-175.
[7]	Bokobza S M, Ye L, Kynaston H G, et al. GDF-9 promotes the growth of prostate cancer cells by protecting them from apoptosis[J]. J Cell Physiol, 2010, 225:529-536.
[8]	Du P, Ye L, Li H, et al. Growth differentiation factor-9 expression is inversely correlated with an aggressive behaviour in human bladder cancer cells[J]. Int J Mol Med, 2011, 29:428-434.
[9]	Yang S D, Sun R C, Mu H J, et al. The expression and clinical significance of TGF-beta1 and MMP2 in human renal clear cell carcinoma[J]. Int J Surg Pathol, 2010, 18:85-93.
[10]	Pelletier S, Tanguay S, Lee S, et al. TGF-alpha as a candidate tumor antigen for renal cell carcinomas[J]. Cancer Immunol Immunother, 2009, 58:1207-1218.
[11]	Helmy A, Hammam O A, El Lithy T R, et al. The role of TGF-beta-1 protein and TGF-beta-R-1 receptor in immune escape mechanism in bladder cancer[J]. MedGenMed, 2008, 9:34.
[12]	Margulis V, Maity T, Zhang X Y, et al. Type III transforming growth factor-beta (TGF-beta) receptor mediates apoptosis in renal cell carcinoma independent of the canonical TGF-beta signaling pathway[J]. Clin Cancer Res, 2008, 14:5722-5730.
[13]	Chen D, Zhao M, Mundy G R. Bone morphogenetic proteins[J]. Growth Factors, 2004, 22:233-241.
[14]	Blanco Calvo M, Bolos Fernandez V, Medina Villaamil V, et al. Biology of BMP signalling and cancer[J]. Clin Transl Oncol, 2009, 11:126-137.
[15]	Bokobza S M, Ye L, Kynaston H G, et al. Growth and differentiation factor-9 promotes adhesive and motile capacity of prostate cancer cells by up-regulating FAK and Paxillin via Smad dependent pathway[J]. Oncol Rep, 2010, 24:1653-1659.
[16]	Ye L, Bokobza S, Li J, et al. Bone morphogenetic protein-10 (BMP-10) inhibits aggressiveness of breast cancer cells and correlates with poor prognosis in breast cancer[J]. Cancer Sci, 2010, 101:2137-2144.
[17]	Wu J B, Fu H Q, Huang L Z, et al. Effects of siRNA-targeting BMP-2 on the abilities of migration and invasion of human liver cancer SMMC7721 cells and its mechanism[J]. Cancer Gene Ther, 2011, 18:20-25.
[18]	Le Page C, Puiffe M L, Meunier L, et al. BMP-2 signaling in ovarian cancer and its association with poor prognosis[J]. J Ovarian Res, 2009, 2:4.
[19]	Bobinac D, Maric I, Zoricic S, et al. Expression of bone morphogenetic proteins in human metastatic prostate and breast cancer[J]. Croat Med J, 2005, 46:389-396.
[20]	Ye L, Kynaston H, Jiang W G. Bone morphogenetic protein-9 induces apoptosis in prostate cancer cells, the role of prostate apoptosis response-4[J]. Mol Cancer Res, 2008, 6:1594-1606.
[21]	Brubaker K D, Corey E, Brown L G, et al. Bone morphogenetic protein signaling in prostate cancer cell lines[J]. J Cell Biochem, 2004, 91:151-160.
[22]	Ye L, Kynaston H, Jiang W G. Bone morphogenetic protein-10 suppresses the growth and aggressiveness of prostate cancer cells through a Smad independent pathway[J]. J Urol, 2009, 181:2749-2759.
[23]	Su Y Q, Sugiura K, Wigglesworth K, et al. Oocyte regulation of metabolic cooperativity between mouse cumulus cells and oocytes:BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells[J]. Development, 2008, 135:111-121.