Oncotarget

Research Papers:

BTG1 expression correlates with pathogenesis, aggressive behaviors and prognosis of gastric cancer: a potential target for gene therapy

Hua-chuan Zheng _, Jing Li, Dao-fu Shen, Xue-feng Yang, Shuang Zhao, Ya-zhou Wu, Yasuo Takano, Hong-zhi Sun, Rong-jian Su, Jun-sheng Luo and Wen-feng Gou

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Oncotarget. 2015; 6:19685-19705. https://doi.org/10.18632/oncotarget.4081

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Abstract

Hua-chuan Zheng1, Jing Li2, Dao-fu Shen1, Xue-feng Yang1, Shuang Zhao1, Ya-zhou Wu1, Yasuo Takano3, Hong-zhi Sun1, Rong-jian Su4, Jun-sheng Luo1, Wen-feng Gou1

1Cancer 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

2Department of Gastroenterology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China

3School of Health Science, Tokyo University of Technology, Ohta-ku, Tokyo, Japan

4Experimental Center, Liaoning Medical University, Jinzhou, China

Correspondence to:

Wen-feng Gou, e-mail: xiaogouaeiou@163.com

Keywords: gastric cancer, BTG1, pathobiological behaviors, carcinogenesis, gene therapy

Received: March 11, 2015     Accepted: May 23, 2015     Published: June 05, 2015

ABSTRACT

Here, we found that BTG1 overexpression inhibited proliferation, migration and invasion, induced G2/M arrest, differentiation, senescence and apoptosis in BGC-823 and MKN28 cells (p < 0.05). BTG1 transfectants showed a higher mRNA expression of Cyclin D1 and Bax, but a lower mRNA expression of cdc2, p21, mTOR and MMP-9 than the control and mock (p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG1 transfectants showed lower mRNA viability and higher apoptosis than the control in both time- and dose-dependent manners (p < 0.05) with the hypoexpression of chemoresistance-related genes (slug, CD147, GRP78, GRP94, FBXW7 TOP1, TOP2 and GST-π). BTG1 expression was restored after 5-aza-2′-deoxycytidine treatment in gastric cancer cells. BTG1 expression was statistically lower in gastric cancer than non-neoplastic mucosa and metastatic cancer in lymph node (p < 0.05). BTG1 expression was positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, TNM staging and worse prognosis (p < 0.05). The diffuse-type carcinoma showed less BTG1 expression than intestinal- and mixed-type ones (p < 0.05). BTG1 overexpression suppressed tumor growth and lung metastasis of gastric cancer cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that down-regulated BTG1 expression might promote gastric carcinogenesis partially due to its promoter methylation. BTG1 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer.


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