RETINOIC ACIDS DIFFERENTIALLY REGULATE NOR-1 AND ITS CLOSELY-RELATED ORPHAN NUCLEAR RECEPTOR GENES IN BREAST-CANCER CELL-LINE MCF-7

NOR-1, NGFI-B, and Nurr1 are closely related orphan nuclear receptors implicated in diverse biological processes including cell growth and d ifferentiation. We examined the effect of retinoic acids on the expres sion of these putative transcription factor genes in the breast cancer cell line MCF-7 by a quantitative reverse transcription and polymeras e chain reaction. Both all-trans and 9-cis retinoic acids markedly ind uced NOR-1 mRNA and slightly increased Nurr1 mRNA. In contrast, NGFI-B mRNA was decreased. In the presence of cycloheximide, all-trans retin oic acid superinduced NOR-1 mRNA, whereas all-trans and 9-cis retinoic acids strongly suppressed the NGPI-B mRNA accumulation. The different ial effects of retinoic acids on the expression of these genes are in contrast with the effects of forskolin and 12-O-tetradecanoylphorbol-1 3-acetate, both of which induced mRNAs of all three genes. These findi ngs suggest that NOR-1, NGFI-B, and Nurr1 play distinct roles in the r etinoic acid signaling in MCF-7 cells. (C) 1997 Academic Press.