甾体类受体共激活因子3基因在结直肠癌中的表达与扩增及其意义

目的探讨甾体类受体共激活因子3(SRC-3)基因在结直肠癌(CRCs)中的蛋白表达与基因扩增及其临床病理学意义。方法运用免疫组织化学和荧光原位杂交方法对60例结直肠癌组织中SRC-3基因的表达与扩增进行检测,结合其临床病理学资料,分析它们之间的相关性。结果在60例CRC患者中,有23例(38%)肿瘤组织出现SRC-3蛋白的过度表达,而且与肿瘤的临床分期有显著的相关性(P<0.01),62%的DukesC或D期CRC呈现出SRC-3蛋白的过度表达;而74%早期(DukesA或B期)的CRC则表现为SRC-3蛋白的正常表达。在荧光原位杂交实验中,有47例的CRC组织的荧光信号得以成功检测,其中6例(13%)CRC出现SRC-3基因高水平的扩增,而且全部出现SRC-3蛋白的过度表达;9例(19%)为SRC-3基因低水平的扩增,其中6例呈现SRC-3蛋白的过度表达;余下的32例无SRC-3基因扩增的CRC中,仍有9例(28%)肿瘤组织出现SRC-3蛋白的过度表达。91%的SRC-3蛋白过度表达者中同时出现P53蛋白的过度表达。结论SRC-3基因的异常和过度表达可能通过影响P53基因的功能,在CRC的发生发展中起着重要的作用;在SRC-3基因表达的调控中,可能存在着SRC-3基因扩增以外的其他调节机制。

Expression and amplification of steroid receptor coactivator-3 gene in colorectal carcinoma and its clinicopathological significance

OBJECTIVE: To investigate the expression and amplification of steroid receptor coactivator- 3(SRC- 3) gene in colorectal carcinoma (CRC) and its clinicopathological significance. METHODS: Immunohistochemistry and fluorescence in situ hybridization (FISH) were used to detect the expression and amplification of SRC- 3 gene in CRC, and its association with patient's clinical pathological features was analyzed. RESULTS: A total of 60 patients with CRC were studied. SAR- 3 proteins were overexpressed in 23 cases (38% ). There was a significant association between SAR- 3 overexpression and neoplasm staging (P< 0.01). SRC- 3 protein was overexpressed in 62% of patients with Dukes C or D stage, whereas SRC- 3 protein was normally expressed in 74% of patients with Dukes A or B stage. As for FISH study, 47 cases were informative. High- level amplification of SRC- 3 gene was detected in 6 cases(13% ) and all showed overexpression of SRC- 3 protein. Low- level amplification of SRC- 3 was observed in 9 cases (19% ). Overexpression of SRC- 3 was detected in 6 cases. The remaining 9 of 32 patients(28% ) without amplification of SRC- 3 gene were observed with overexpression of SRC- 3 protein. In addition, 91% patients with CRC were found oversxpression of SRC- 3 as well as overexpression of P53. CONCLUSION: The abnormal expression of SRC- 3 gene might impact on the function of P53 and development of CRC. There might exist some unknown mechanisms other than gene amplification of SRC- 3 to regulate its encoded protein expression in CRC.