PI-3K and Akt are mediators of AP-1 induction by 5-MCDE in mouse epidermal Cl41 cells

被引:49
作者
Li, JX
Chen, HB
Tang, MS
Shi, XL
Amin, S
Desai, D
Costa, M
Huang, CS
机构
[1] NYU, Sch Med, Nelson Inst Environm Med, Tuxedo Pk, NY 10987 USA
[2] Chinese Acad Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China
[3] Amer Hlth Fdn, Ctr Canc, Inst Canc Prevent, Valhalla, NY 10595 USA
关键词
polycyclic aromatic hydrocarbons; signal transduction; protein kinases; transcription factor; tumor promotion;
D O I
10.1083/jcb.200401004
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
5-Methylchrysene has been found to be a complete carcinogen in laboratory animals. However, the tumor promotion effects of (+/-)-anti-5-methylchrysene-1,2-diol-3,4-epoxide (5-MCDE) remain unclear. In the present work, we found that 5-MCDE induced marked activator protein-1 (AP-1) activation in Cl41 cells. 5-MCDE also induced a marked activation of phosphatidylinositol 3-kinase (PI-3K). Inhibition of PI-3K impaired 5-MCDE-induced AP-1 transactivation, suggesting that PI-3K is an upstream kinase involved in AP-1 activation by 5-MCDE. Furthermore, we found that Akt is a PI-3K downstream mediator for 5-MCDE-induced AP-1 transactivation, whereas another PI-3K downstream kinase, p70(S6K), was not involved in AP-1 activation by 5-MCDE. Moreover, inhibition of Akt activation blocked 5-MCDE-induced activation of extracellular signal-regulated protein kinases (ERKs) and c-Jun NH2-terminal kinases (JNKs), whereas it did not affect p38K activation. Consistently, overexpression of a dominant-negative mutant of ERK2 or JNK1 blocked the AP-1 activation by 5-MCDE. These results demonstrate that 5-MCDE is able to induce AP-1 activation, and the AP-1 induction is specifically through a PI-3K/Akt-dependent and p70(S6K)-independent pathway.
引用
收藏
页码:77 / 86
页数:10
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