Abstract
Pulses (up to 2 h) of the adrenocorticotropic hormone (ACTH) rapidly activate p42 and p44 MAPK (5 min), induce the c-Fos protein (1 h, 80% of cells) and stimulate entry of mouse Y-1 adrenocortical cells into the S phase of the cell cycle. This set of sequential events is also triggered in Y-1 cells by bFGF, and reflects a mitogenic response to ACTH. We report here that 90% inhibition of c-fos mRNA translation with a c-fos antisense oligodeoxynucleotide completely blocks the entry of Y1 cells into S phase stimulated by pulses of ACTH. These results indicate that c-Fos protein is an intracellular mediator of the mitogenic response to ACTH.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenal Cortex Neoplasms / genetics
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Adrenal Cortex Neoplasms / metabolism
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Adrenal Cortex Neoplasms / pathology
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Adrenocorticotropic Hormone / antagonists & inhibitors
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Adrenocorticotropic Hormone / pharmacology*
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Animals
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DNA / biosynthesis
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Fibroblast Growth Factors / pharmacology
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Mice
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Mitogens / antagonists & inhibitors
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Mitogens / pharmacology*
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Oligonucleotides, Antisense / pharmacology
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-fos / physiology*
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Proto-Oncogene Proteins c-jun / genetics
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S Phase / drug effects
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / metabolism
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Tumor Cells, Cultured / pathology
Substances
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Mitogens
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Oligonucleotides, Antisense
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Proto-Oncogene Proteins c-fos
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Proto-Oncogene Proteins c-jun
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Fibroblast Growth Factors
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Adrenocorticotropic Hormone
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DNA