Expression and clinical significance of transforming growth factor β receptor Ⅰ and Smad4 in renal carcinoma
-
摘要: 目的:探讨转化生长因子β受体Ⅰ(TGF-βRⅠ)及Smad4在肾透明细胞癌(RCCC)及癌旁组织中的蛋白表达情况及临床意义。方法:采用免疫组织化学P-V法分别检测58例RCCC组织、36例癌旁组织中TGF-βRⅠ和Smad4蛋白表达情况,并分析其表达水平与RCCC临床病理特征的关系。结果:①TGF-βRⅠ蛋白在RCCC、癌旁组织的阳性表达率分别为51.7%、80.6%,差异有统计学意义(P<0.05);Smad4蛋白在RCCC、癌旁组织的阳性表达率分别为56.9%、86.1%,差异有统计学意义(P<0.05)。②TGF-βRⅠ和Smad4蛋白在RCCC组织中的表达均与性别、年龄无关(P>0.05),而与肿瘤病理分级及临床分期相关(P<0.05)。③TGF-βRⅠ和Smad4蛋白表达呈正相关。结论:①TGF-βRⅠ、Smad4在RCCC中的表达降低,提示TGF-βRⅠ、Smad4的表达缺失可能参与了RCCC的发生、发展。②TGF-βRⅠ与Smad4之间存在正相关,说明这两种因子在TGF-β信号通路中相互作用,共同参与了RCCC的发生、发展及转移。
-
关键词:
- 肾透明细胞癌 /
- 转化生长因子β受体Ⅰ /
- Smad4蛋白 /
- 免疫组织化学
Abstract: Objective: To investigate the expression of transforming growth factor β receptor Ⅰ (TGF-βRⅠ) and Smad4 in specimens of renal clear cell carcinoma (RCCC) and peritumoral tissues and to study their clinical significance.Method: Immunohistochemistry was used to investigate the protein expression of TGF-βRⅠand Smad4 in 58 cases of RCCC and 36 cases of peritumoral tissues and their relationship with the clinical pathologic characteristics of RCCC was analyzed.Result: ①The positive expression rates of TGF-βRⅠ in RCCC and peritumoral tissues were 51.7%, 80.6% respectively, which showed a statistical difference (P<0.05). The positive expression rates of Smad4 in RCCC and peritumoral tissues were 56.9%, 86.1% respectively, which was a statistical difference (P<0.05). ②The expressions of TGF-βRⅠ and Smad4 protein were correlated with neither gender nor age (P>0.05), whereas they were closely associated with clinical stages and pathologic grades (P<0.05). ③There existed a positive correlation between the expression of TGF-βRⅠand Smad4.Conclusion: ①Lower expression levels of TGF-βRⅠand Smad4 may be contributed to formation and progression of RCCC. ②TGF-βRⅠpositively correlates with Smad4. Moreover, their interaction may contribute to formation, invasion and metastasis of RCCC. -
-
[1] Yamamura Y, Hua X, Bergelson S, et al. Critical role of Smads and AP-1 complex in transforming growth factor-beta-dependent apoptosis[J]. J Biol Chem, 2000, 275(46):36295-36302.
[2] Chen W, Fu X B, Sheng Z Y. Review of current progress in the structure and function of Smad protein[J]. Chinese Medical Journal, 2002, 115(3):446-450.
[3] Subramanian G, Schwarz R E, Higgins L, et al. Targeting endogenous transforming growth factor beta receptor signaling in SMAD4-deficient pancreatic carcinoma cells inhibits their invasive phenotype l[J]. Cancer Res, 2004, 64(15):5200-5211.[ZK)]
[4] Shi Y. Structural insights on Smad function in TGF beta signaling[J]. Bioessays, 2001, 23(3):223-232.
[5] Kinugasa S, Abe S, Tachibnaa M, et al. Overexpression of transforming growth factor-β in Scirrhous carcinoma of the Stomach correlates with decreased survival[J]. Oncology, 1998, 55(6):528-587.
[6] Wang J, Sun L, Myeroff L, et al. Demonstration that mutation of the type II transforming growth factor beta receptor inactivates its tumor suppressor activity in replication error-positive colon carcinoma cells[J]. J Biol Chem, 1995, 270(37):22044-22049.
[7] Kim Y H, Lee H S, Lee H J, et al. Prognostic significance of the expression of smad4 and smad7 in human gastric carcinomas[J]. Ann Oncol, 2004, 15(4):574-580.
[8] Hahn S A, Schutte M, Shmsul T M, et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1[J]. Science, 1996, 271(5247):350-353.
[9] Tascilar M, Skinner H G, Rosty C, et al. The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma[J]. Clin Cancer Res, 2001, 7(12):4115-4121.
[10] Kang Y, Mariano J M, Angdisen J, et al. Enhanced tumorigenesis and reduced transforming growth factor-beta type II receptor in lung tumors from mice with reduced gene dosage of transforming growth factor-beta 1[J]. Mol Carcinog, 2000, 29(2):112-126.
[11] Barrett M T, Schutte M, Kern S E, et al. Allelic loss and mutational analysis of the DPC4 gene in esophageal adenocarcinoma[J]. Cancer Res, 1996, 56(19):4351-4353.
-
计量
- 文章访问数: 122
- PDF下载数: 108
- 施引文献: 0