ACTH-induced c-myc proto-oncogene expression precedes antimitogenic effect during differentiation of fetal rat adrenocortical cells.
The regulation of proto-oncogenes has been connected with proliferation and differentiation in various cell types. In the present study, the ACTH-induced expression of c-myc mRNA and proliferation of fetal rat adrenocortical cells have been studied. Low levels of c-myc mRNA were detected in undifferentiated zona glomerulosa-like cells. Stimulation with ACTH for 2 to 6 h transiently increased the c-myc mRNA levels. Both basal and ACTH-induced expression levels were increased by the protein synthesis inhibitor cycloheximide. Treatment with a protein kinase C (PKC) activator 12-0-tetradecanoyl phorbol-13-acetate mimicked the effect of ACTH, whereas c-myc mRNA levels decreased by inhibiting the PKC with H-7. ACTH inhibited proliferation of fetal rat adrenocortical cells during the first 24 h of stimulation. The inhibitory effect began from 6 h, reached its maximum at 12 h and slowly vanished at 24 h. Our data demonstrated that ACTH transiently increased c-myc mRNA expression. Adrenocortical c-myc expression was mediated via PKC. In contrast to previous reports, where c-myc expression precedes proliferation of various cells, ACTH-induced c-myc mRNA expression of cultured fetal rat adrenocortical cells was followed by inhibition of proliferation.
Heikkilä
P
P
Department of Pathology, University of Helsinki, Finland.
Arola
J
J
Salmi
A
A
Kahri
A I
AI
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental; D016259:Genes, myc; D007150:Immunohistochemistry; D007546:Isoquinolines / Q000494:pharmacology; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007546:Isoquinolines; D015345:Oligonucleotide Probes; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000324:Adrenocorticotropic Hormone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate