The effects of the insulin-like growth factors and transforming growth factor beta on the Jun proto-oncogene family in MC3T3-E1 cells.
Previous studies have demonstrated that when cells of the mouse osteoblastic cell line MC3T3-E1 are exposed to IGF-I and IGF-II they exhibit rapid and transient induction of the transcript from the proto-oncogene c-fos [8]. To clarify the relationship between induction of cell proliferation and proto-oncogene expression in MC3T3-E1 cells, the acute affects of IGF-I and IGF-II, growth factors that stimulate cell proliferation, and of TGF-beta 1, which inhibits cell proliferation, northern analyses with cDNA-derived probes for the proto-oncogenes c-jun, jun-B, and jun-D were undertaken. Concurrent northern analyses with a probe for c-fos extended our previous results to include the effect of TGF-beta 1 on c-fos. IGF-I does not induce the c-jun, jun-B, or jun-D transcripts, the former and latter being produced at detectable levels constitutively. After 1 hour of exposure to IGF-II the c-jun transcript response ranges from onefold to 13-fold and the jun-D transcript response ranges around two-fold. After 1 hour of exposure to TGF-beta 1, the jun-B transcript response ranges from eightfold to 24-fold, the c-fos transcript response ranges between sixfold and sevenfold. The differences observed in the magnitude and kinetics of the induction provoked by these growth factors is consistent with the presence of a regulatory circuit acting through the Jun family members which may act to stimulate transcription differentially when bound to DNA either as homodimers or, with Fos family proteins, as heterodimers.
Strong
D D
DD
Department of Medicine, Loma Linda University, California 92357.
Merriman
H L
HL
Landale
E C
EC
Baylink
D J
DJ
Mohan
S
S
D016475:3T3 Cells; D000818:Animals; D016762:Genes, fos; D016758:Genes, jun / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II