Peng Zhihai, Tang Huamei, Wang Xiaoliang, Zhou Chongzhi, Fan Junwei, Wang Liwei, Jia Zhiliang, Li Qiang, Le Xiangdong, Wei Daoyan, Xie Keping
Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, PR China.
Int J Oncol. 2008 Nov;33(5):979-84.
Recent studies demonstrated an epigenetic inactivation of the runt-related transcription factor 3 (RUNX3) gene in human colon cancer. However, it remains unclear whether RUNX3 is tumor suppressive in colon cancer and, if so, the underlying molecular mechanisms of this activity are still unknown. In the present study, we sought to determine the level of RUNX3 expression in human colon tumor specimens and used an animal model of colon cancer to determine the impact of RUNX3 expression on tumor growth and metastasis. First, we analyzed RUNX3 expression in 83 human colon tumor specimens using immunohistochemical, reverse transcriptase-polymerase chain reaction, and Western blot analysis. RUNX3 mRNA and protein expression levels were consistently lower in tumor tissue specimens than in matched normal colon tissue specimens. Also, restoration of RUNX3 expression in colon cancer cells using gene transfer inhibited colon tumor growth and metastasis in our animal model, which was consistent with inhibition of colon tumor growth in vitro. Collectively, our clinical and experimental data support the notion that RUNX3 is a tumor suppressor in human colon cancer.
近期研究表明，人类结肠癌中与矮小相关的转录因子3（RUNX3）基因存在表观遗传失活。然而，RUNX3在结肠癌中是否具有肿瘤抑制作用仍不清楚，即便如此，这种作用的潜在分子机制也尚不明确。在本研究中，我们试图确定RUNX3在人类结肠肿瘤标本中的表达水平，并利用结肠癌动物模型来确定RUNX3表达对肿瘤生长和转移的影响。首先，我们采用免疫组织化学、逆转录聚合酶链反应和蛋白质印迹分析，对83例人类结肠肿瘤标本中的RUNX3表达进行了分析。肿瘤组织标本中RUNX3 mRNA和蛋白质表达水平始终低于匹配的正常结肠组织标本。此外，在我们的动物模型中，利用基因转移恢复结肠癌细胞中RUNX3的表达可抑制结肠肿瘤的生长和转移，这与体外抑制结肠肿瘤生长的结果一致。总体而言，我们的临床和实验数据支持RUNX3是人类结肠癌肿瘤抑制因子这一观点。
