Carcinogenesis Advance Access originally published online on January 23, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis, Vol. 25, No. 6, 881-887,
June 2004
Carcinogenesis vol.25 no.6 © Oxford University Press 2004; all rights reserved.
ARTICLE |
Id-1-induced Raf/MEK pathway activation is essential for its protective role against taxol-induced apoptosis in nasopharyngeal carcinoma cells
1 Cancer Biology Group, Department of Anatomy and 2 Faculty of Medicine, Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Hong Kong
3 To whom correspondence should be addressed. Email: xhwang{at}hkucc.hku.hk
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Tang, P. Hirsch, F. Fava, S. Lapusan, C. Marzac, I. Teyssandier, J. Pardo, J.-P. Marie, and O. Legrand High Id1 expression is associated with poor prognosis in 237 patients with acute myeloid leukemia Blood, October 1, 2009; 114(14): 2993 - 3000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kashiwakura, K. Ochiai, M. Watanabe, F. Abarzua, M. Sakaguchi, M. Takaoka, R. Tanimoto, Y. Nasu, N.-h. Huh, and H. Kumon Down-regulation of Inhibition of Differentiation-1 via Activation of Activating Transcription Factor 3 and Smad Regulates REIC/Dickkopf-3-Induced Apoptosis Cancer Res., October 15, 2008; 68(20): 8333 - 8341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sittler, J. Zhou, J. Park, N. K. Yuen, S. Sarantopoulos, J. Mollick, R. Salgia, A. Giobbie-Hurder, G. Dranoff, and F. S. Hodi Concerted Potent Humoral Immune Responses to Autoantigens Are Associated with Tumor Destruction and Favorable Clinical Outcomes without Autoimmunity Clin. Cancer Res., June 15, 2008; 14(12): 3896 - 3905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Caldon, A. Swarbrick, C. S.L. Lee, R. L. Sutherland, and E. A. Musgrove The Helix-Loop-Helix Protein Id1 Requires Cyclin D1 to Promote the Proliferation of Mammary Epithelial Cell Acini Cancer Res., April 15, 2008; 68(8): 3026 - 3036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Lefranc, V. Facchini, and R. Kiss Proautophagic Drugs: A Novel Means to Combat Apoptosis-Resistant Cancers, with a Special Emphasis on Glioblastomas Oncologist, December 1, 2007; 12(12): 1395 - 1403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, M.-T. Ling, Q. Wang, C.-K. Lau, S. C. L. Leung, T. K. Lee, A. L. M. Cheung, Y.-C. Wong, and X. Wang Identification of a Novel Inhibitor of Differentiation-1 (ID-1) Binding Partner, Caveolin-1, and Its Role in Epithelial-Mesenchymal Transition and Resistance to Apoptosis in Prostate Cancer Cells J. Biol. Chem., November 16, 2007; 282(46): 33284 - 33294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Li, P. Y. Cheung, X. Wang, S. W. Tsao, M. T. Ling, Y. C. Wong, and A. L.M. Cheung Id-1 activation of PI3K/Akt/NF{kappa}B signaling pathway and its significance in promoting survival of esophageal cancer cells Carcinogenesis, November 1, 2007; 28(11): 2313 - 2320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhang, W. E. Lawson, V. V. Polosukhin, A. Pozzi, T. S. Blackwell, Y. Litingtung, and C. Chiang Inhibitor of Differentiation 1 Promotes Endothelial Survival in a Bleomycin Model of Lung Injury in Mice Am. J. Pathol., October 1, 2007; 171(4): 1113 - 1126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-J. Kim, H. Chung, Y.-G. Yoo, H. Kim, J.-Y. Lee, M.-O. Lee, and G. Kong Inhibitor of DNA Binding 1 Activates Vascular Endothelial Growth Factor through Enhancing the Stability and Activity of Hypoxia-Inducible Factor-1{alpha} Mol. Cancer Res., April 1, 2007; 5(4): 321 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Skobeleva, S. Menon, L. Weber, E. A. Golemis, and V. Khazak In vitro and in vivo synergy of MCP compounds with mitogen-activated protein kinase pathway- and microtubule-targeting inhibitors Mol. Cancer Ther., March 1, 2007; 6(3): 898 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-J. Lih, W. Wei, and S. N. Cohen Txr1: a transcriptional regulator of thrombospondin-1 that modulates cellular sensitivity to taxanes Genes & Dev., August 1, 2006; 20(15): 2082 - 2095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-T. Ling, W.-K. Kwok, M. K. Fung, W. Xianghong, and Y.-C. Wong Proteasome mediated degradation of Id-1 is associated with TNF{alpha}-induced apoptosis in prostate cancer cells Carcinogenesis, February 1, 2006; 27(2): 205 - 215. [Abstract] [Full Text] [PDF]
|
|