Phorbol ester mimics ACTH action in corticoadrenal cells stimulating steroidogenesis, blocking cell cycle, changing cell shape, and inducing c-fos proto-oncogene expression.
Cells of the Y-1 corticoadrenal line are: (a) functional, (b) cell cycle-arrested by adrenocorticotropic hormone (ACTH), (c) tumorigenic, and (d) c-Ki-ras overexpressing. We here report that the phorbol ester phorbol 12-myristate 13-acetate (PMA) mimics all ACTH-specific effects in Y-1 cells, namely: (a) steroid-ogenesis stimulation, (b) cell cycle block, and (c) cell shape change. In addition, both ACTH and PMA caused a rapid and transient induction of the c-fos proto-oncogene while having no effect on c-Ki-ras mRNA steady state levels. Dibutyryl cAMP, known to elicit ACTH effects in Y-1 cells, was a poor inducer of the c-fos gene. PMA pretreatment rendered Y-1 cells unresponsive to ACTH. These results suggest that protein kinase C is likely to be involved in the mechanisms of action of ACTH.
Kimura
E
E
Departamento de Bioquímica, Universidade de São Paulo, Brasil.
Armelin
H A
HA
D000306:Adrenal Cortex Neoplasms; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D007700:Kinetics; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D013755:Tetradecanoylphorbol Acetate