Chengqi Guan and Hui Shi contributed equally to this work.
Article first published online: 16 APR 2013
Copyright © 2013 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 6, pages 1343–1354, June 2013
How to Cite
Guan, C., Shi, H., Wang, H., Zhang, J., Ni, W., Chen, B., Hou, S., Yang, X., Shen, A. and Ni, R. (2013), CtBP2 contributes to malignant development of human esophageal squamous cell carcinoma by regulation of p16INK4A. J. Cell. Biochem., 114: 1343–1354. doi: 10.1002/jcb.24475
All the authors declare no conflict of interest.
- Issue published online: 16 APR 2013
- Article first published online: 16 APR 2013
- Accepted manuscript online: 17 DEC 2012 08:21AM EST
- Manuscript Accepted: 28 NOV 2012
- Manuscript Received: 22 APR 2012
- National Basic Research Program of China. Grant Numbers: 2011CB910604, 2012CB822104
- National Natural Science Foundation of China. Grant Number: 81272708 and 31070723
- Natural Science Foundation of Jiangsu province. Grant Number: BK2009157
- Key Project Natural Science Foundation of Jiangsu University and College. Grant Number: 11KJA310002
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Nantong University Graduate Student Science and Technology Innovation Project. Grant Number: YKC12013
- C-TERMINAL BINDING PROTEIN 2 (CtBP2);
- ESOPHAGEAL SQUAMOUS CELL CARCINOMA (ESCC);
- MALIGNANT DEVELOPMENT;
C-terminal binding protein-2 (CtBP2), as a transcriptional co-repressor, has been shown to mediate the repression of p16INK4A, a tumor suppressor gene product, in primary human cells. Here we aimed to investigate how the correlation between CtBP2 and p16INK4A influenced the development of esophageal squamous cell carcinoma (ESCC). Immunohistochemistry of ESCC tissue sections indicated that the CtBP2 and p16INK4A expressions were inversely correlated to each other with a linear regression coefficient of −0.747 (P < 0.05), and Western blot analysis revealed that CtBP2 was higher expressed in tumorous tissues than in adjacent non-tumorous tissues. Either CtBP2 or p16INK4A expression was significantly related to histological differentiation (P = 0.016 or 0.001) and to the expression of Ki-67, a proliferating marker (P = 0.006 or 0.02), and patients with higher CtBP2 and lower p16INK4A expressions had shorter overall survival. We also observed that CtBP2 modulated the cell proliferation and cell cycle in ECA109 cells, an ESCC cell line, by inhibiting p16INK4A. Overexpression or knockdown of CtBP2 in ECA109 cells was found to inhibit or activate the mRNA or protein expression of p16INK4A, which in turn altered the cell proliferation and cell cycle in ECA109 cells, as measured by flow cytometry and cell count assay. Additionally, after ECA109 cells silenced for CtBP2 were treated with cisplatin (an anti-ESCC agent), the p16INK4A expression was up-regulated, and the cell apoptosis was promoted, thus confirming the repression of p16INK4A by CtBP2. Collectively, all results suggested that CtBP2 might contribute to the progression of ESCC through a negative transcriptional regulation of p16INK4A. J. Cell. Biochem. 114: 1343–1354, 2013. © 2013 Wiley Periodicals, Inc.