Activation of Pro-apoptotic p38-MAPK Pathway in the Prostate Cancer Cell Line M12 Expressing a Truncated IGF-IR

J. Wu, K. Haugk, S. R. Plymate*

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The type I insulin-like growth factor receptor (IGF-IR) plays a critical role in signaling survival and proliferation in many cell types. Activation of IGF-IR by its ligands promotes cell proliferation via mitogen-activated protein kinase (MAPK) cascade and cell survival via phosphoinositide 3-kinase (PI3K) cascade. The IGF-IR emerges as a powerful growth factor for many tumor cells. A truncated IGF-IR 486/STOP, described as a dominant negative IGF-IR mutant, was shown to induce apoptosis and inhibit tumor growth in vivo while endogenous IGF-IR was activated. To investigate the mechanism(s) of the action of 486/STOP, we have introduced 486/STOP into the prostate tumor model cell line M12 and its derivative M12lisn that expresses high levels of wild type IGF-IR. We have found that 486/STOP induces apoptosis in M12 and M12lisn cells in culture and that 486/STOP acts through activation of the pro-apoptotic p38-MAPK without interfering with wild type IGF-IR activation. In addition, our results have indicated that 486/STOP induced activation of p38-MAPK increases through activation of endogenous IGF-IR. These data suggest that activation of the IGF-IR by 486/STOP can selectively enhance the previously reported IGF-IR pro-apoptotic signaling pathways.

Original languageEnglish (US)
Pages (from-to)751-757
Number of pages7
JournalHormone and Metabolic Research
Volume35
Issue number11-12
DOIs
StatePublished - Nov 2003

Keywords

  • 486/STOP
  • ERK
  • Insulin-like Growth Factor I (IGF-I)
  • PI3K
  • pAkt

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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