Transcriptional up-regulation of restin by all-trans retinoic acid through STAT1 in cancer cell differentiation process.
RESTIN, a member of the melanoma-associated antigen superfamily, is a nuclear protein induced by atRA (all-trans retinoic acid) in HL60 cells. HeLa cells stably transfected with restin results in G1 cell cycle arrest. How this gene is regulated by atRA in the cell differentiation process is still unclear. In this study, we observed that up-regulation of restin was present during the atRA-induced HL60 cell differentiation process, suggesting the functional relevance between RESTIN and atRA-induced cellular effects. In order to further define the transcriptional regulation of restin by atRA, we analyzed the promoter region of restin. About 2.1kb 5' flanking sequence of this gene was cloned into vector pGL3 and its core promoter region was identified through systemic deletions. Interestingly, restin promoter containing several potential consensus-binding sites of STAT-1alpha was activated by atRA in ER(+) MCF-7 cells but not in ER(-) MDA-MB-231 cells, over-expression of STAT-1alpha in latter rescued the activation effect of restin promoter in response to atRA and IFNgamma. Our evidence supported that STAT-1alpha plays an important role in the atRA-induced transcriptional up-regulation of restin, which was associated with the atRA-induced HL60 cell differentiation and potentially mediated the downstream effects of atRA signal pathway via STAT-1alpha in some cancer cells.
Fu
Haiyan
H
Department of Biochemistry and Molecular Biology, State Key Lab of Cancer Biology, Fourth Military Medical University, Xi'an 710032, PR China.
Yang
Guodong
G
Lu
Fan
F
Wang
Ruihua
R
Yao
Libo
L
Lu
Zifan
Z
D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D001483:Base Sequence; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3 / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation
D000951:Antigens, Neoplasm; D050832:Interferon-Stimulated Gene Factor 3; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; C079868:gamma interferon activation factor; C076744:cytoplasmic linker protein 170; D014212:Tretinoin