Department of Health Sciences Faculty Articles

Retinoic Acid Inhibition of Serum-Induced C-Fos Transcription in a Fibrosarcoma Cell Line.

Document Type

Article

Publisher

American Association for Cancer Research

ISSN

0008-5472

Publication Date

5-1992

Keywords

Cell Division, Cycloheximide, Down-Regulation, Fibrosarcoma, Neoplastic, Genes, fos, Half-Life, RNA, Signal Transduction, Transcription, Genetic, Tumor Cells, Cultured

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.

Volume

52

Issue

9

First Page

2384

Last Page

2388

Disciplines

Medicine and Health Sciences

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