Abnormal expression of GADD45B in human colorectal carcinoma

Journal of Translational Medicine

Research

Yayun Chi¹  Xiuying Xiao²  Xiaoyan Zhou³  Lisha Wang³  Dali Li³  Yiqin Wang³  Cong Tan³  Shujuan Ni³  Xiang Du⁴  Ping Wei⁵ 

[1] Cancer Research Institute, Fudan University Shanghai Cancer Center, 200032, Shanghai, China;Department of Pathology, Fudan University Shanghai Cancer Center, 200032, Shanghai, China;Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China;Department of Oncology, Shanghai Xuhui District Center Hospital, 200031, Shanghai, China;Department of Pathology, Fudan University Shanghai Cancer Center, 200032, Shanghai, China;Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China;Institute of Pathology, Fudan University, 200032, Shanghai, China;Department of Pathology, Fudan University Shanghai Cancer Center, 200032, Shanghai, China;Department of Oncology, Shanghai Medical College, Fudan University, 200032, Shanghai, China;Institute of Pathology, Fudan University, 200032, Shanghai, China;Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China;Department of Pathology, Fudan University Shanghai Cancer Center, 200032, Shanghai, China;Institute of Pathology, Fudan University, 200032, Shanghai, China;

关键词: Colorectal carcinoma;    GADD45B;    Carcinogenesis;    Relapse;   

DOI  :  10.1186/1479-5876-10-215

 received in 2012-07-11, accepted in 2012-10-18,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundGADD45B is a member of the growth arrest DNA damage-inducible gene family associated with cell growth control, apoptosis, and DNA damage repair response. The aim of this study is to detect the role of GADD45B in colorectal carcinoma (CRC); the area not studied in depth to date.MethodsThe mRNA and protein levels of GADD45B were examined by Real-Time quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) in CRC tissues and adjacent noncancerous tissues (ANCT). Over-expression plasmids and SiRNA were used to regulate GADD45B expression in CRC cell lines in vitro and flow cytometry and Western blotting were used to detect apoptotic changes.ResultsThe mRNA and protein levels of GADD45B were significantly higher in CRC tissues than those in ANCT (P<0.05). Up-regulation of GADD45B was also correlated with relapse and death of CRC patients (P<0.05). The Kaplan-Meier survival curves indicated that disease-free survival (DFS) was significantly worse in CRC patients who showed GADD45B overexpression. A Cox multivariate analysis revealed that GADD45B overexpression and TNM stage were significant factors affecting patients’ survival. On the other hand, as a tumor suppressor gene, GADD45B amplified from normal colorectal tissues could induce apoptosis in CRC cell lines and may be associated with the p53-mediated apoptotic pathways.ConclusionGADD45B, a tumor suppressor gene potentially through the p53-mediated apoptotic pathways, is paradoxically overexpressed in CRC and as such may play an unappreciated role in tumorigenesis. The exact mechanism of GADD45B inactivation and overexpression requires further investigation. GADD45B could be a potential therapeutic target for CRC treatment in future.

【 授权许可】

Unknown   
© Wang et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.