转化生长因子-β抑制因子SnoN和Ski与人类结直肠癌发生有关。
TGF-beta repressors SnoN and Ski are implicated in human colorectal carcinogenesis.
作者信息
Bravou Vasiliki, Antonacopoulou Anna, Papadaki Helen, Floratou Konstantina, Stavropoulos Michalis, Episkopou Vasso, Petropoulou Chariklia, Kalofonos Haralabos
机构信息
Clinical Oncology Laboratory, School of Medicine, University of Patras, Rio Patras, Greece.
出版信息
Cell Oncol. 2009;31(1):41-51. doi: 10.3233/clo-2009-0460.
BACKGROUND
The TGF-beta 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 beta-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.
背景
转化生长因子-β（TGF-β）信号转导抑制因子SnoN和Ski与人类癌症密切相关。
方法
为探究SnoN和Ski在结直肠癌发生发展过程中的作用，我们通过免疫组织化学方法检测了一系列人类结直肠腺瘤、癌及淋巴结转移灶中它们的蛋白表达谱。同时，采用实时逆转录聚合酶链反应（Real-Time RT-PCR）对SnoN的mRNA表达进行定量分析。
结果
SnoN和Ski在重度发育异常的腺瘤及结直肠癌中均呈过表达。蛋白表达定位于细胞质和细胞核，以细胞质为主。亚细胞定位与结直肠癌的病理变量存在不同程度的相关性。虽然蛋白水平与肿瘤侵袭和转移无显著相关性，但观察到细胞核内的SnoN和Ski与β-连环蛋白信号通路存在显著相关性。此外，与正常对照相比，癌组织中SnoN mRNA无差异，且SnoN蛋白水平与mRNA水平无相关性。
结论
我们的研究结果表明，SnoN和Ski在人类结直肠癌发生过程中发挥致癌作用，其过表达与疾病早期相关。
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