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Hormonal modulation of c-fos expression in isolated hepatocytes. Effects of angiotensin II and phorbol myristate acetate on transcription and mRNA degradation

Hormonal modulation of c-fos expression in isolated hepatocytes. Effects of angiotensin II and phorbol myristate acetate on transcription and mRNA degradation

Biochimica et Biophysica Acta 1310(2): 217-222

ISSN/ISBN: 0006-3002

PMID: 8611636

DOI: 10.1016/0167-4889(95)00168-9

It has been shown that angiotensin II and PMA increase the expression of proto-oncogenes (c-fos, c-myc and c-mos) in liver cells. In this study the effects of angiotensin II and PMA on c-fos transcription and mRNA stability were investigated. Using nuclear run-off transcription assays, it was observed that PMA and angiotensin II induced a rapid increase in c-fos transcription. The transcription rate of the GAPDH gene did not change, indicating that the effects were not general on gene transcription. The ability of these agents to modulate proto-oncogene mRNA stability was tested by measuring c-fos mRNA half-life. It was observed that c-fos mRNA half-life was relatively short (approximately 14-18 min) and that angiotensin II and PMA markedly stabilized mRNA, increasing its half-life (approximately 4-fold and approximately 2-fold, respectively). The protein synthesis inhibitor cycloheximide increased mRNA stability to a much greater extent. Our results clearly demonstrate that angiotensin II and PMA increased c-fos mRNA accumulation in liver cells through two actions: induction of c-fos gene transcription and increase in mRNA stability.

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Accession: 008782257

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