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HDAC2 overexpression confers oncogenic potential to human lung cancer cells by deregulating expression of apoptosis and cell cycle proteins.
MedLine Citation:
PMID:  22492270     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Histone deacetylase 2 (HDAC2) is crucial for embryonic development, affects cytokine signaling relevant for immune responses, and is often significantly overexpressed in solid tumors, but little is known of its role in human lung cancer. In this study, we demonstrated the aberrant expression of HDAC2 in lung cancer tissues and investigated oncogenic properties of HDAC2 in human lung cancer cell lines. HDAC2 inactivation resulted in regression of tumor cell growth and activation of cellular apoptosis via p53 and Bax activation and Bcl2 suppression. In cell cycle regulation, HDAC2 inactivation caused induction of p21(WAF1/CIP1) expression, and simultaneously suppressed the expressions of cyclin E2, cyclin D1, and CDK2, respectively. Consequently, this led to the hypophosphorylation of pRb protein in G1/S transition and thereby inactivated E2F/DP1 target gene transcriptions of A549 cells. In addition, we demonstrated that HDAC2 directly regulated p21(WAF1/CIP1) expression in a p53-independent manner. However, HDAC1 was not related to p21(WAF1/CIP1) expression and tumorigenesis of lung cancer. Lastly, we observed that sustained-suppression of HDAC2 in A549 lung cancer cells attenuated in vitro tumorigenic properties and in vivo tumor growth of the mouse xenograft model. Taken together, we suggest that the aberrant regulation of HDAC2 and its epigenetic regulation of gene transcription in apoptosis and cell cycle components play an important role in the development of lung cancer. J. Cell. Biochem. 113: 2167-2177, 2012. © 2012 Wiley Periodicals, Inc.
Authors:
Kwang Hwa Jung; Ji Heon Noh; Jeong Kyu Kim; Jung Woo Eun; Hyun Jin Bae; Hong Jian Xie; Young Gyoon Chang; Min Gyu Kim; Hanna Park; Jung Young Lee; Suk Woo Nam
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  113     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-04-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2167-77     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Affiliation:
Department of Pathology, College of Medicine and Functional RNomics Research Center, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul, Korea; Functional RNomics Research Center, The Catholic University of Korea, Seoul, Korea.
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