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

Jingxia Li, Haobin Chen, Moon Shong Tang, Xianglin Shi, Shantu Amin, Dhimant Desai, Max Costa, Chuanshu Huang

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


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, p70S6K, 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.

Original languageEnglish (US)
Pages (from-to)77-86
Number of pages10
JournalJournal of Cell Biology
Issue number1
StatePublished - Apr 12 2004

All Science Journal Classification (ASJC) codes

  • Cell Biology


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