title: Retinoic acid inhibition of serum-induced c-fos transcription in a fibrosarcoma cell line.
abstract: We investigated the mechanism by which retinoic acid causes growth arrest and flat reversion of SSV-NRK, simian sarcoma virus-transformed normal rat kidney cells. Northern analysis revealed that both chronic (7 days) and acute (6 h) retinoic acid treatment of serum-stimulated SSV-NRK cells caused a 6-fold decrease in c-fos mRNA levels. In addition, nuclear run-on experiments showed that retinoic acid regulated c-fos expression in SSV-NRK cells at the transcriptional initiation level. Attenuation of c-fos transcription was equal in both retinoic acid-treated and control cells, and no increased c-fos mRNA turnover was detected in retinoic acid-treated cells. Furthermore, there was no observed change in the c-fos mRNA levels after only 30 min of retinoic acid treatment, suggesting that a mechanism involving the interruption of the signal transduction mechanism at the membrane level is unlikely. Because it has been shown that c-fos expression plays a pivotal role in mitogenesis of quiescent fibroblasts, we conclude that the retinoic acid-mediated down-regulation of c-fos expression is a mechanism for growth inhibition in SSV-NRK cells.
authors.affiliation: Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
authors.forename: P
authors.initials: P
authors.lastname: Jaffey
authors.forename: L N
authors.initials: LN
authors.lastname: Chan
authors.forename: J
authors.initials: J
authors.lastname: Shao
authors.forename: J
authors.initials: J
authors.lastname: Schneider-Schaulies
authors.forename: T S
authors.initials: TS
authors.lastname: Chan
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation; D005354:Fibrosarcoma / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016762:Genes, fos; D006207:Half-Life; D012333:RNA, Messenger / Q000032:analysis* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D014212:Tretinoin; D003513:Cycloheximide