TGF-beta repressors SnoN and Ski are implicated in human colorectal carcinogenesis.
TGF-beta repressors SnoN and Ski are implicated in human colorectal carcinogenesis.
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DOI：
10.3233/clo-2009-0460
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Kalofonos H
中科院分区：
文献类型：
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作者：
Bravou V;Antonacopoulou A;Papadaki H;Floratou K;Stavropoulos M;Episkopou V;Petropoulou C;Kalofonos H
背景：转化生长因子-β信号抑制因子SnoN和Ski与人类癌症密切相关。方法：为探讨SnoN和Ski在结直肠癌发生发展中的作用，采用免疫组织化学方法检测了SnoN和Ski在结直肠腺瘤、癌和淋巴结转移中的蛋白表达。用Real-time RT-PCR检测SnoN的mRNA表达。结果：SnoN和Ski在伴有重度不典型增生的腺瘤和结直肠癌中均有高表达。蛋白表达以胞浆和胞核为主，以胞浆定位为主。亚细胞定位与结直肠癌的病理变量有不同的关系。虽然蛋白水平与肿瘤的侵袭和转移无明显相关性，但核SnoN和Ski的表达与β-连环蛋白通路密切相关。此外，癌组织中SnoN基因的表达与正常组织相比无明显差异，且SnoN蛋白与基因表达水平之间无相关性。结论：SnoN和Ski在人类结直肠癌发生中起致癌作用，其过表达与早期疾病有关。
Background: The TGF-β signaling repressors SnoN and Ski have been critically implicated in human cancer. Methods: To explore the role of SnoN and Ski in the development and progression of colorectal cancer we examined their protein expression profile by immunohistochemistry in a series of human colorectal adenomas, carcinomas and lymph node metastases. The mRNA expression of SnoN was also quantified by Real-Time RT-PCR. Results: SnoN and Ski were overexpressed both in adenomas with severe dysplasia and colorectal carcinomas. Protein expression was cytoplasmic and nuclear with predominant cytoplasmic localization. The subcellular localization was related differently to pathologic variables of colorectal carcinomas. Although there was no significant association of protein levels with tumor invasion and metastasis, a significant correlation of nuclear SnoN and Ski with β-catenin pathway was observed. Moreover, SnoN mRNA did not differ in carcinomas as compared to normal control and there was no correlation between SnoN protein and mRNA levels. Conclusion: Our findings suggest that SnoN and Ski exert oncogenic effects in human colorectal carcinogenesis and their overexpression is implicated in early stage disease.