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PMID: 3540941 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Insulin and growth factor effects on c-fos expression in normal and protein kinase C-deficient 3T3-L1 fibroblasts and adipocytes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 24 ·1986-12-00 ·Pages 9453-7

Stumpo DJ, Blackshear PJ

Abstract

We investigated the expression of the protooncogene c-fos in 3T3-L1 fibroblasts and adipocytes in response to a variety of growth-promoting agents in normal cells and in cells preincubated with phorbol esters to deplete them of protein kinase C. There was a rapid accumulation of c-fos mRNA in fibroblasts and adipocytes treated with phorbol 12-myristate 13-acetate, platelet-derived growth factor, fibroblast growth factor, fetal calf serum, bombesin, and insulin, especially in the adipocytes. Phorbol 12-myristate 13-acetate pretreatment abolished the increase in c-fos mRNA due to additional phorbol 12-myristate 13-acetate treatment and decreased but did not eliminate the ability of platelet-derived growth factor, fibroblast growth factor, fetal calf serum, bombesin, and insulin to stimulate c-fos mRNA. These data suggested that c-fos mRNA could be induced in serum-deprived 3T3-L1 fibroblasts and adipocytes by at least two separate pathways, one involving protein kinase C and the other independent of protein kinase C. In the very insulin-sensitive 3T3-L1 adipocytes, insulin rapidly and transiently increased c-fos expression (c-fos mRNA appeared by 15 min and disappeared after 60 min) via interaction with its own cellular receptor, rather than by interacting with receptors for one of the insulin-like growth factors. Cycloheximide treatment in combination with insulin or phorbol 12-myristate 13-acetate resulted in superinduction of c-fos mRNA. We conclude that insulin can rapidly stimulate c-fos mRNA accumulation in 3T3-L1 adipocytes and that part of the growth factor-stimulated increase in this mRNA that occurs in protein kinase C-deficient cells may be due to activation of a pathway similar or identical to that activated by insulin.

MeSH Terms
Adipose Tissue/cytology Animals Cycloheximide/pharmacology Fibroblasts Gene Expression Regulation/drug effects Growth Substances/pharmacology Insulin/pharmacology Insulin-Like Growth Factor I/pharmacology Insulin-Like Growth Factor II/pharmacology Mice Protein Kinase C/deficiency Proto-Oncogene Proteins/genetics Proto-Oncogenes RNA, Messenger/genetics Tetradecanoylphorbol Acetate/pharmacology
Chemicals
Growth Substances Insulin Proto-Oncogene Proteins RNA, Messenger Insulin-Like Growth Factor I Insulin-Like Growth Factor II Cycloheximide Protein Kinase C Tetradecanoylphorbol Acetate
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Stumpo D J
Blackshear P J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.83.24.9453
Published
1986-12-00
Pages
9453-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC387156
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.83.24.9453 PMC Full Text View journal details
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