title: Retinoic acid downregulates growth, fibronectin and RAR alpha in 3T3 cells: Ha-ras blocks this response and RA metabolism.
abstract: Retinoic acid (RA) reduced growth, fibronectin, and retinoic acid receptor (RAR alpha) in NIH 3T3 cells but not in cells transformed by the Ha-ras oncogene. RA lowered RAR alpha transcript and protein, increased RAR beta transcripts, and had no effect on RAR gamma. H-ras transformation downregulated RAR expression and abolished responsiveness to RA. Ha-ras-transformed cells were as active as normal NIH-3T3 cells in RA uptake but were unable to degrade it to medium oxidation product, so that, paradoxically, the resistant cells accumulated 20-30-fold as much RA as the sensitive cells. RA sensitivity/insensitivity correlated with RA metabolism/lack thereof in 15 cell lines in serum-free medium. These data suggest a relationship between RA inhibition of cell growth and intracellular RA metabolism.
authors.affiliation: Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: De Luca
authors.forename: G
authors.initials: G
authors.lastname: Scita
authors.forename: J
authors.initials: J
authors.lastname: Takatsuka
mesh_terms: D016475:3T3 Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism*; D011905:Genes, ras / Q000502:physiology; D051379:Mice; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D005353:Fibronectins; D018168:Receptors, Retinoic Acid; D014212:Tretinoin