TY - JOUR
T1 - Retinoic acid downregulates growth, fibronectin and RARα in 3T3 cells
T2 - Ha-ras blocks this response and RA metabolism
AU - De Luca, Luigi M.
AU - Scita, Giorgio
AU - Takatsuka, Jun
PY - 1997/11/1
Y1 - 1997/11/1
N2 - 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.
AB - 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.
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U2 - 10.1002/(SICI)1097-4652(199711)173:2<297::AID-JCP39>3.0.CO;2-A
DO - 10.1002/(SICI)1097-4652(199711)173:2<297::AID-JCP39>3.0.CO;2-A
M3 - Article
C2 - 9365540
AN - SCOPUS:0030728152
SN - 0021-9541
VL - 173
SP - 297
EP - 300
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 2
ER -