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 at-rest. How this gene is regulated by atRA in file 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 2.1 kb 5' ranking 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 coil sensus-binding sites of STAT-la was activated by atRA in ER+ MCF-7 cells but not in ER- MDA-MB-231 cells, over-expression or STAT-1 alpha in latter rescued the activation effect of restin promoter in response to atRA and IFN gamma. Ourevidence Supported that STAT-1 alpha plays all 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-1 alpha in some cancer cells. (c) 2006 Elsevier Inc. All rights reserved.