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Retinoic acid downregulates growth, fibronectin and RARα in 3T3 cells: Ha‐ras blocks this response and RA metabolism
Author(s) -
De Luca Luigi M.,
Scita Giorgio,
Takatsuka Jun
Publication year - 1997
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199711)173:2<297::aid-jcp39>3.0.co;2-a
Subject(s) - retinoic acid , fibronectin , 3t3 cells , cell culture , intracellular , cell growth , cell , retinoic acid receptor , microbiology and biotechnology , metabolism , downregulation and upregulation , oncogene , biology , chemistry , endocrinology , biochemistry , transfection , cell cycle , gene , genetics
Retinoic acid (RA) reduced growth, fibronectin, and retinoic acid receptor (RARα) in NIH 3T3 cells but not in cells transformed by the Ha‐ras oncogene. RA lowered RARα transcript and protein, increased RARβ transcripts, and had no effect on RARγ. 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 products, 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. J. Cell. Physiol. 173:297–300, 1997. Published 1997 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.