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Activation of MAPK signaling pathway is essential for Id-1 induced serum independent prostate cancer cell growth

Oncogene volume 21, pages 8498–8505 (2002)Cite this article

Abstract

The helix–loop–helix protein Id-1 has been suggested to play a positive role in cell proliferation and tumorigenesis of many types of human cancers. However, little is known about the molecular mechanism involved in the function of Id-1. In this study, using four stable Id-1 transfectant clones, we investigated the involvement of MAPK signaling pathway in the Id-1 induced serum independent prostate cancer cell growth. Our results demonstrated that both transient and stable ectopic Id-1 expression in prostate cancer LNCaP cells led to activation of the Raf/MEK1/2 signaling pathway. In addition, inhibition of MEK1/2 phosphorylation by one of its inhibitors, PD098059, resulted in the decreased cell cycle S phase fraction and cell growth rate, suggesting that activation of MAPK signaling pathway is essential for Id-1 induced prostate cancer cell proliferation. Furthermore, treatment with antisense oligonucleotide complementary to Id-1 mRNA in PC-3 and DU145 cells resulted in a decreased Id-1 expression which was accompanied by decreased Egr-1 protein. Our results suggest for the first time that the function of Id-1 is associated with MAPK signaling pathway activation and indicate a possible novel mechanism in which Id-1 regulates prostate cancer cell growth and tumorigenesis.

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Acknowledgements

This work was supported by RGC grants to YC Wong (HKU 7186/99M and HKU 7314/01M) and Area of Excellence Scheme (Project No. AoE/P-10/01).

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Authors and Affiliations

  1. Department of Anatomy, Cancer Biology Laboratory, Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China

    Ming-Tat Ling, Xianghong Wang, Xue-Song Ouyang, Tian-Yong Fan, Kexin Xu, Sai-Wah Tsao & Y C Wong

  2. Department of Surgery, The University of Hong Kong, Hong Kong, SAR, China

    Terence KW Lee

  3. Central Laboratory of the Institute of Molecular Technology or Drug Discovery and Synthesis, The University of Hong Kong, Hong Kong, SAR, China

    Sai-Wah Tsao & Y C Wong

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  1. Ming-Tat Ling
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Correspondence to Y C Wong.

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Ling, MT., Wang, X., Ouyang, XS. et al. Activation of MAPK signaling pathway is essential for Id-1 induced serum independent prostate cancer cell growth. Oncogene 21, 8498–8505 (2002). https://doi.org/10.1038/sj.onc.1206007

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