Retinoic acid inhibition of insulin-like growth factor I stimulation of c-fos mRNA levels in a breast carcinoma cell line.
Retinoic acid (RA) inhibits insulin-like growth factor I (IGF-I)-stimulated growth of the human breast carcinoma cell line MCF-7. RA-mediated inhibition of IGF-I-stimulated growth is not associated with either a decrease in IGF-I receptor number or affinity. Since IGF-I modulation of c-fos gene expression appears to be an important step in IGF-I-mediated cellular proliferation, we investigated whether RA inhibits IGF-I stimulation of c-fos mRNA levels. Treatment of MCF-7 cells with IGF-I resulted in an approximately 10-fold increase in c-fos mRNA levels. Pretreatment of MCF-7 cells with 1 microM RA blocked IGF-I-mediated enhancement of c-fos mRNA levels by approximately 70%. The maximal RA effect (80% inhibition) on IGF-I stimulation of c-fos mRNA levels was noted within 2 h of exposure to RA. IGF-I did not modulate the c-fos gene promoter and appears to increase the stability of the c-fos mRNA. Preexposure of cells to RA results in a significant decrease (P < 0.05) in c-fos mRNA stability. The half-life of c-fos mRNA in the IGF-I-treated cells is 53 +/- 6 6 min while that in RA-pretreated cells is 27 +/- 0.4 min. We conclude that RA-mediated inhibition of IGF-I stimulation of c-fos mRNA may represent a potential mechanism by which RA inhibits IGF-I stimulation of growth.
Li
X S
XS
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201.
Chen
J C
JC
Sheikh
M S
MS
Shao
Z M
ZM
Fontana
J A
JA
D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis* / Q000187:drug effects / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014212:Tretinoin; D007334:Insulin-Like Growth Factor I