The roles of BTG3 expression in gastric cancer: a potential marker for carcinogenesis and a target molecule for gene therapy.

// Wen-feng Gou 1 , Xue-feng Yang 1 , Dao-fu Shen 1 , Shuang Zhao 1 , Yun-peng Liu 2 , Hong-zhi Sun 1 , Yasuo Takano 3 , Rong-jian Su 4 , Jun-sheng Luo 1 and Hua-chuan Zheng 1 1 Cancer Research Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China 2 Department of Oncological Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China 3 School of Health Science, Tokyo University of Technology, Ohta-ku, Tokyo 4 Experimental Center, Liaoning Medical University, Jinzhou, China Correspondence to: Hua-chuan Zheng, email: // Keywords : gastric cancer, BTG3, carcinogenesis, pathobiological behaviors, gene therapy Received : February 11, 2015 Accepted : March 10, 2015 Published : March 30, 2015 Abstract BTG (B-cell translocation gene) can inhibit cell proliferation, metastasis and angiogenesis, cell cycle progression, and induce differentiation in various cells. Here, we found that BTG3 overexpression inhibited proliferation, induced S/G2 arrest, differentiation, autophagy, apoptosis, suppressed migration and invasion in MKN28 and MGC803 cells ( p < 0.05). BTG3 transfectants showed a higher mRNA expression of p27, Bax, 14-3-3, Caspase-3, Caspase-9, Beclin 1, NF-κB, IL-1, -2, -4, -10 and -17, but a lower mRNA expression of p21, MMP-9 and VEGF than the control and mock ( p < 0.05). At protein level, BTG3 overexpression increased the expression of CDK4, AIF, LC-3B, Beclin 1 and p38 ( p < 0.05), but decreased the expression of p21 and β-catenin in both transfectants ( p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG3 transfectants showed lower viability and higher apoptosis than the control in both time- and dose-dependent manners ( p < 0.05). BTG3 expression was restored after 5-aza-2’-deoxycytidine or MG132 treatment in gastric cancer cells. BTG3 expression was decreased in gastric cancer in comparison to the adjacent mucosa ( p < 0.05), and positively correlated with venous invasion and dedifferentiation of cancer ( p < 0.05). It was suggested that BTG3 expression might contribute to gastric carcinogenesis. BTG3 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer.