Document Detail


PAX2 protein induces expression of cyclin D1 through activating AP-1 protein and promotes proliferation of colon cancer cells.
MedLine Citation:
PMID:  23135283     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Paired box (PAX) 2, a transcription factor, plays a critical role in embryogenesis. When aberrantly expressed in adult tissues, it generally exhibits oncogenic properties. However, the underlying mechanisms remain unclear. We reported previously that the expression of PAX2 was up-regulated in human colon cancers. However, the role of PAX2 in colon cancer cells has yet to be determined. The aim of this study is to determine the function of PAX2 in colon cancer cells and to investigate the possible mechanisms underlain. We find that knockdown of PAX2 inhibits proliferation and xenograft growth of colon cancer cells. Inhibition of PAX2 results in a decreased expression of cyclin D1. Expression of cyclin D1 is found increased in human primary colon malignant tumors, and its expression is associated with that of PAX2. These data indicate that PAX2 is a positive regulator of expression of cyclin D1. We find that knockdown of PAX2 inhibits the activity of AP-1, a transcription factor that induces cyclin D1 expression, implying that PAX2 induces cyclin D1 through AP-1. PAX2 has little effect on expression of AP-1 members including c-Jun, c-Fos, and JunB. Our data show that PAX2 prevents JunB from binding c-Jun and enhances phosphorylation of c-Jun, which may elevate the activity of AP-1. Taken together, these results suggest that PAX2 promotes proliferation of colon cancer cells through AP-1.
Authors:
Hai-Sheng Zhang; Bing Yan; Xue-Bing Li; Li Fan; Yun-Fang Zhang; Guo-Hao Wu; Min Li; Jing Fang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-07
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-31     Completed Date:  2013-03-25     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  44164-72     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Tumor
Cell Proliferation*
Colonic Neoplasms / genetics,  metabolism*,  physiopathology
Cyclin D1 / genetics*,  metabolism
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
PAX2 Transcription Factor / genetics,  metabolism*
Proto-Oncogene Proteins c-fos / genetics,  metabolism*
Proto-Oncogene Proteins c-jun / genetics,  metabolism*
Transcription Factor AP-1 / genetics,  metabolism
Up-Regulation*
Chemical
Reg. No./Substance:
0/PAX2 Transcription Factor; 0/PAX2 protein, human; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/Transcription Factor AP-1; 136601-57-5/Cyclin D1
Comments/Corrections

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