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

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

Research output: Journal article publicationJournal articleAcademic researchpeer-review

89 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)8498-8505
Number of pages8
JournalOncogene
Volume21
Issue number55
DOIs
Publication statusPublished - 5 Dec 2002
Externally publishedYes

Keywords

  • Cell growth
  • Id-1
  • MAPK
  • Prostate cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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