BTG1 might be employed as a biomarker for carcinogenesis and a target for gene therapy in colorectal cancers

作者：Zhao, Shuang; Chen, Shu-rui; Yang, Xue-feng; Shen, Dao-fu; Takano, Yasuo; Su, Rong-jian; Zheng, Hua-chuan^*

来源：Oncotarget, 2017, 8(5): 7502-7520.

DOI：10.18632/oncotarget.10649

• colorectal cancer
• BTG1
• carcinogenesis
• aggressive phenotypes
• gene therapy

Here, BTG1 overexpression inhibited proliferation, induced differentiation, autophagy, and apoptosis in colorectal cancer cells (p<0.05). BTG1 overexpression reduced mitochondrial membrane potential and caused senescence in HCT-116 transfectants (p<0.05). BTG1-induced G(2) arrest might be related to Cyclin B1 and Cdc25B hypoexpression in HCT-15 transfectants, while G(1) arrest in HCT-116 transfectants overexpressing p21 and p27. BTG1 overexpression decreased the expression of Bcl-2, Bcl-xL, XIAP, Akt1 or survivin and increased the expression of Bax or p53 in colorectal cancer cells. BTG1-induced autophagy was dependent on Beclin-1 expression. BTG1 overexpression might weaken beta-catenin pathway in colorectal cancer cells. The chemosensitivity of BTG1 transfectants to paclitaxel, cisplatin, MG132 or SAHA was positively correlated with its apoptotic induction. There was a lower expression level of BTG1 in cancer than matched non-neoplastic mucosa by RT-PCR (p<0.05), while versa for Western blot and immunohistochemical data (p<0.05). BTG1 overexpression significantly suppressed the growth of HCT-15 and HCT-116 via inhibiting proliferation, inducing apoptosis and autophagy in nude mice. Up-regulated BTG1 expression plays an important role in colorectal carcinogenesis as a potential biomarker. BTG1 expression might reverse aggressive phenotypes, so it might be employed as a target of gene therapy for colorectal cancer.

• 出版日期2017-1-31
• 单位锦州医科大学