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Regulation of Nur77 expression by β‐catenin and its mitogenic effect in colon cancer cells
Author(s) -
Wu Hua,
Lin Yayu,
Li Wengang,
Sun Zhe,
Gao Weiwei,
Zhang Haiping,
Xie Lei,
Jiang Fuquan,
Qin Bin,
Yan Tingdong,
Chen Liqun,
Zhao Yi,
Cao Xihua,
Wu Yin,
Lin Bingzhen,
Zhou Hu,
Wong Alice SzeTsai,
Zhang XiaoKun,
Zeng JinZhang
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-166462
Subject(s) - nerve growth factor ib , wnt signaling pathway , cancer research , cancer cell , colorectal cancer , cancer , biology , microbiology and biotechnology , signal transduction , nuclear receptor , transcription factor , biochemistry , gene , genetics
The orphan nuclear receptor Nur77 is an immediate‐early response gene whose expression is rapidly induced by various extracellular stimuli. The aims of this study were to study the role of Nur77 expression in the growth and survival of colon cancer cells and the mechanism by which Nur77 expression was regulated. We showed that levels of Nur77 were elevated in a majority of human colon tumors (9/12) compared to their nontumorous tissues and that Nur77 expression could be strongly induced by different colonic carcinogens including deoxycholic acid (DCA). DCA‐induced Nur77 expression resulted in up‐regulation of antiapoptotic BRE and angiogenic VEGF, and it enhanced the growth, colony formation, and migration of colon cancer cells. In studying the mechanism by which Nur77 was regulated in colon cancer cells, we found that β‐catenin was involved in induction of Nur77 expression through its activation of the tran‐scriptional activity of AP‐1 (c‐Fos/c‐Jun) that bound to and transactivated the Nur77 promoter. Together, our results demonstrate that Nur77 acts to promote the growth and survival of colon cancer cells and serves as an important mediator of the Wnt/β‐catenin and AP‐1 signaling pathways.—Wu, H., Lin, Y., Li, W., Sun, Z., Gao, W., Zhang, H., Xie, L., Jiang, F., Qin, B., Yan, T., Chen, L., Zhao, Y., Cao, X., Wu, Y., Lin, B., Zhou, H., Wong, A.S.‐T., Zhang, X.‐K., Zeng, J.‐Z. Regulation of Nur77 expression by β‐catenin and its mitogenic effect in colon cancer cells. FASEB J. 25, 192–205 (2011). www.fasebj.org