title: Regulation of Nur77 expression by β-catenin and its mitogenic effect in colon cancer cells.
abstract: 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 transcriptional 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.
authors.affiliation: Institute for Biomedical Research, Xiamen University, Xiamen 361005, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
authors.forename: Yayu
authors.initials: Y
authors.lastname: Lin
authors.forename: Wengang
authors.initials: W
authors.lastname: Li
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sun
authors.forename: Weiwei
authors.initials: W
authors.lastname: Gao
authors.forename: Haiping
authors.initials: H
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Xie
authors.forename: Fuquan
authors.initials: F
authors.lastname: Jiang
authors.forename: Bin
authors.initials: B
authors.lastname: Qin
authors.forename: Tingdong
authors.initials: T
authors.lastname: Yan
authors.forename: Liqun
authors.initials: L
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xihua
authors.initials: X
authors.lastname: Cao
authors.forename: Yin
authors.initials: Y
authors.lastname: Wu
authors.forename: Bingzhen
authors.initials: B
authors.lastname: Lin
authors.forename: Hu
authors.initials: H
authors.lastname: Zhou
authors.forename: Alice Sze-Tsai
authors.initials: AS
authors.lastname: Wong
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Zhang
authors.forename: Jin-Zhang
authors.initials: JZ
authors.lastname: Zeng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002470:Cell Survival; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003840:Deoxycholic Acid / Q000633:toxicity; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018808:Transcription Factor AP-1; D051176:beta Catenin; D003840:Deoxycholic Acid; D019869:Phosphatidylinositol 3-Kinases; D048031:JNK Mitogen-Activated Protein Kinases