The H-ras oncogene interferes with retinoic acid signaling and metabolism in NIH3T3 cells.
We have previously shown that retinoic acid (RA) fails to induce transglutaminase C in H-ras transformed NIH-3T3 cells. Therefore, we investigated the effect of the H-ras oncogene on the metabolism of RA and on the expression of the cellular RA-binding protein I mRNA. HPLC analysis of the media and cell extracts demonstrated that H-ras-transformed cells metabolize RA to a much lesser extent than control cells, resulting in a higher concentration of RA in H-ras cells. Although inactive in endogenous transglutaminase induction, H-ras cell-associated RA was shown to be biologically available to induce activation of a reporter construct containing a retinoid response element and in stimulating transglutaminase activity in nontransfected cells. Cellular RA-binding protein I mRNA, supposedly involved in RA storage, was significantly increased in the H-ras-transformed cells. These data demonstrate that, even though H-ras-transformed cells accumulate up to 20 fold the concentration of RA as NIH-3T3 cells, they fail to show transglutaminase induction, suggesting that H-ras interferes with signal transduction by RA.
Kósa
K
K
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255, USA.
Jones
C S
CS
De Luca
L M
LM
D016475:3T3 Cells / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D011905:Genes, ras / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology*; D014316:Tritium
D003470:Culture Media; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082927:retinoic acid binding protein I, cellular; C082928:retinoic acid binding protein II, cellular; D014316:Tritium; D014212:Tretinoin