Journal Article

Id-1-induced Raf/MEK pathway activation is essential for its protective role against taxol-induced apoptosis in nasopharyngeal carcinoma cells

Hiu Wing Cheung, Ming-tat Ling, Sai Wah Tsao, Y.C. Wong and Xianghong Wang

in Carcinogenesis

Volume 25, issue 6, pages 881-887
Published in print June 2004 | ISSN: 0143-3334
Published online June 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh087
Id-1-induced Raf/MEK pathway activation is essential for its protective role against taxol-induced apoptosis in nasopharyngeal carcinoma cells

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Increasingly, evidence supports the function of the helix–loop–helix protein Id-1 (inhibitor of differentiation/DNA binding-1) as an oncogene. Over-expression of Id-1 is not only observed in many types of human cancer but its expression levels have been correlated with cancer progression. However, little is known about the molecular mechanisms responsible for the function of Id-1. Recently, we and others reported that Id-1-induced cell proliferation was mediated through a Raf/MEK signalling pathway. In this study, we investigated if ectopic Id-1 expression in nasopharyngeal carcinoma cells had any protective effect on taxol-induced death, which is also regulated through Raf/MEK pathway. Using four stable Id-1 transfectant clones, we found that exogenous Id-1 expression led to phosphorylation of Raf-1 and MEK1/2 kinases, which was associated with resistance to taxol. Treatment of the Id-1 expressing cells with a MEK inhibitor, PD098059, resulted in an increased taxol-induced apoptosis rate in Id-1 transfectants compared with the vector control. In addition, the fact that the taxol-induced apoptosis rate, down-regulation of Bcl-2 and up-regulation of Bax were suppressed by PD098059 treatment in Id-1 expressing cells indicates that the Id-1 induced cellular protection against apoptosis is mediated through Raf/MEK signalling pathways. Our results suggest that Id-1 may be an upstream regulator of the Raf/MEK signalling pathway, which plays an essential role in protection against taxol-induced apoptosis. Our evidence also indicates a novel treatment strategy to increase anticancer drug-induced apoptosis through inactivation of the Id-1 protein.

Keywords: EBV, Epstein–Barr virus; MMT, 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide; NPC, nasopharyngeal carcinoma; SFM, serum-free medium

Journal Article.  5136 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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