14-3-3σ mediation of cell cycle progression is p53-independent in response to insulin-like growth factor-I receptor activation

Yang Zhang, Michael Karas, Hong Zhao, Shoshana Yakar, Derek LeRoith

Research output: Contribution to journalArticle

Abstract

We investigated the role of 14-3-3σ protein in insulin-like growth factor-I (IGF-I) receptor signaling. It has been previously shown that 14-3-3σ negatively regulates cell cycle especially in response to p53-sensitive DNA damage. In this study we demonstrated that 14-3-3σ is a positive mediator of IGF-I receptor-induced cell proliferation. Treatment with IGF-I increased 14-3-3σ mRNA and protein levels about 4-fold, in a time-dependent manner in MCF-7 breast cancer cells. Preincubation with the phosphoinositide 3′-kinase inhibitor LY294002 significantly reduced the effects of IGF-I on 14-3-3 σ gene expression in these cells, suggesting that this effect of IGF-I occurs via the phosphoinositide 3′-kinase pathway. 14-3-3σ is induced by IGF-I in MCF-7 cells, which express wild-type p53, as well as in MCF-7 cells transfected with a small interference RNA targeting duplex that reduced p53 expression levels. These results suggest that IGF-I induces 14-3-3σ expression in a manner that is independent of p53. Using the small interference RNA strategy, we demonstrated that a 70-75% reduction of 14-3-3σ mRNA levels resulted in a similar decrease in the effects of IGF-I on cell cycle progression and proliferation in MCF-7 cells. This effect was also associated with a reduction in IGF-I-induced cyclin D1 expression. Taken together, these results suggest that 14-3-3σ positively mediates IGF-I-induced cell cycle progression.

Original languageEnglish (US)
Pages (from-to)34353-34360
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number33
DOIs
StatePublished - Aug 13 2004

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IGF Type 1 Receptor
Insulin-Like Growth Factor I
Cell Cycle
Chemical activation
Cells
MCF-7 Cells
14-3-3 Proteins
1-Phosphatidylinositol 4-Kinase
Phosphatidylinositols
RNA Interference
Phosphotransferases
Cell Proliferation
RNA
Messenger RNA
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Cyclin D1
Cell proliferation
Gene expression
DNA Damage
Breast Neoplasms

ASJC Scopus subject areas

  • Biochemistry

Cite this

14-3-3σ mediation of cell cycle progression is p53-independent in response to insulin-like growth factor-I receptor activation. / Zhang, Yang; Karas, Michael; Zhao, Hong; Yakar, Shoshana; LeRoith, Derek.

In: Journal of Biological Chemistry, Vol. 279, No. 33, 13.08.2004, p. 34353-34360.

Research output: Contribution to journalArticle

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