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Induction of AP-1 activity associated with c-Jun and JunB is required for mitogenesis induced by insulin and vanadate in SV40-transformed 3T3T cells.

Abstract：

:Insulin and vanadate function as complete mitogens for SV40-transformed murine 3T3T (CSV3-1) cells but not for nontransformed 3T3T cells. Mitogenesis induced by insulin and vanadate in CSV3-1 cells is associated with the induction of the expression of protooncogenes c-jun and junB, two major AP-1 transcription factor components. We now report that both insulin and vanadate induce a significant increase in AP-1 DNA binding activity in CSV3-1 cells but not in 3T3T cells. Gel supershift assays and Western blot analysis using specific antibodies demonstrate that the increased AP-1 binding activity induced by insulin and vanadate in CSV3-1 cells is primarily contributed by an increase in the expression of c-Jun and JunB protein levels. Furthermore, treatment of CSV3-1 cells with antisense oligodeoxyribonucleotides to c-jun or to junB blocks insulin- and vanadate-induced mitogenesis whereas antisense junD oligomers have no inhibitory effects. These results therefore demonstrate that the induction of AP-1 binding activity associated with c-Jun and JunB is required for insulin- and vandate-induced mitogenesis in SV40-transformed murine 3T3T cells. Additional data presented in this paper show that JunD/AP-1 binding activity, which is thought to play a negative role in regulating cell proliferation, is also slightly induced following insulin and vanadate stimulation in CSV3-1 cells. Nevertheless, the ratio of proliferation promoting c-Jun/AP-1 and JunB/AP-1 binding activities to proliferation inhibiting JunD/AP-1 binding activity is significantly increased following insulin and vanadate stimulation. These results therefore support the concept that modulation of the balance of positive Jun/AP-1 and negative Jun/AP-1 activities is important in regulating cell proliferation.

journal_name

Mol Cell Biochem

journal_title

Molecular and cellular biochemistry

authors

Wang H,Xie Z,Scott RE

doi

10.1023/a:1006889623326

subject

Has Abstract

pub_date

1997-03-01 00:00:00

pages

21-30

issue

1-2

eissn

0300-8177

issn

1573-4919

journal_volume

168

pub_type

杂志文章

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Induction of AP-1 activity associated with c-Jun and JunB is required for mitogenesis induced by insulin and vanadate in SV40-transformed 3T3T cells.