Role of stimulatory guanine nucleotide binding protein (G(Sα)) in proliferation of PC-3M prostate cancer cells

Jeremy Chien, Girish V. Shah

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Previous studies have shown that calcitonin-like immunoreactive substances are secreted by primary prostate cells. Furthermore, exogenously added calcitonin stimulates proliferation of androgen-responsive LnCaP cells. To examine the possible effect of calcitonin on growth of invasive prostate cancer cells, we tested its effects on proliferation of PC-3M cells. Calcitonin stimulated DNA synthesis of PC-3M cells in a dose-dependent fashion, and also stimulated adenylyl cyclase and protein kinase C activities. To further delineate the role of these signaling cascades in proliferation of PC-3M prostate cancer cells, we selectively activated these pathways by transfecting cDNAs expressing constitutively active forms of either G(s)α (G(s)α-QL) or G(q)α (G(q)α-QL). cDNAs expressing wild-type forms of G-proteins (G(s)α-WT and G(q)α-WT) were used as vehicle controls. G(q)α-QL transfectants exhibited growth inhibition and terminal differentiation. Those expressing G(s)α-QL exhibited a dramatic increase in growth rate. G(s)α-QL transfectants displayed an almost 3-fold increase in [3H]-thymidine incorporation and over a 4-fold increase in growth rate when compared with parental PC-3M cells or those expressing wild-type G(s)α (G(s)α-WT). The growth-promoting action of G(s)α-QL could not be mimicked by either 8-bromo cAMP or forskolin. However, nifedipine, a calcium channel antagonist, potently and selectively inhibited DNA synthesis in G(s)α-QL transfectants. These results suggest that the growth-promoting actions of G(s)α on PC-3M cells may be mediated by nifedipine-sensitive proliferative events. (C) 2001 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)46-54
Number of pages9
JournalInternational Journal of Cancer
Volume91
Issue number1
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • G-protein-cell proliferation
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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