Possible mechanism of CCL2-induced Akt activation in prostate cancer cells

Kosuke Mizutani, Hernan Roca, Zachary Varsos, Kenneth Pienta

Research output: Contribution to journalArticle

Abstract

C-C chemokine ligand 2 (CCL2) is a chemokine that has been demonstrated to play a pivotal role in prostate cancer tumorigenesis and metastasis. These effects are mediated by the ligand binding to the G protein-coupled receptor (GPCR) C-C chemokine receptor 2 (CCR2). It has recently been demonstrated that CCL2 increases Akt phosphorylation in prostate cancer cells, and prevents prostate cancer cells from autophagic death through activation of Akt pathway. The purpose of this study was to determine the mechanism by which CCL2 activates Akt in prostate cancer PC-3 cell line. CCL2-induced phosphorylation of Akt was inhibited by pertussis toxin and the adenylyl cyclase inhibitor SQ22536. Akt phosphorylation was promoted by prior treatment with cholera toxin. The results suggest that CCL2-induced Akt phosphorylation is mediated by the Gαi complex and adenylyl cyclase. This is the first study that demonstrates a direct involvement of adenylyl cyclase in CCL2-induced Akt phosphorylation.

Original languageEnglish (US)
Pages (from-to)3109-3113
Number of pages5
JournalAnticancer Research
Volume29
Issue number8
Publication statusPublished - Aug 2009
Externally publishedYes

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Keywords

  • Adenylyl cyclase
  • CCR2
  • ERK and Rho/ROCK
  • G protein
  • Pertussis toxin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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