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A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion.

Publication ,  Journal Article
Kelly, P; Stemmle, LN; Madden, JF; Fields, TA; Daaka, Y; Casey, PJ
Published in: J Biol Chem
September 8, 2006

Many studies have suggested a role for the members of the G12 family of heterotrimeric G proteins (Galpha12 and Galpha13) in oncogenesis and tumor cell growth. However, few studies have examined G12 signaling in actual human cancers. In this study, we examined the role of G12 signaling in prostate cancer. We found that expression of the G12 proteins is significantly elevated in prostate cancer. Interestingly, expression of the activated forms of Galpha12 or Galpha13 in the PC3 and DU145 prostate cancer cell lines did not promote cancer cell growth. Instead, expression of the activated forms of Galpha12 or Galpha13 in these cell lines induced cell invasion through the activation of the RhoA family of G proteins. Furthermore, inhibition of G12 signaling by expression of the RGS domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) in the PC3 and DU145 cell lines did not reduce cancer cell growth. However, inhibition of G12 signaling with p115-RGS in these cell lines blocked thrombin- and thromboxane A2-stimulated cell invasion. These observations identify the G12 family proteins as important regulators of prostate cancer invasion and suggest that these proteins may be targeted to limit invasion- and metastasis-induced prostate cancer patient mortality.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

September 8, 2006

Volume

281

Issue

36

Start / End Page

26483 / 26490

Location

United States

Related Subject Headings

  • Second Messenger Systems
  • Rho Guanine Nucleotide Exchange Factors
  • Recombinant Fusion Proteins
  • Receptors, G-Protein-Coupled
  • Random Allocation
  • Prostatic Neoplasms
  • Prostate
  • Neoplasm Invasiveness
  • Male
  • Humans
 

Citation

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Kelly, P., Stemmle, L. N., Madden, J. F., Fields, T. A., Daaka, Y., & Casey, P. J. (2006). A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion. J Biol Chem, 281(36), 26483–26490. https://doi.org/10.1074/jbc.M604376200
Kelly, Patrick, Laura N. Stemmle, John F. Madden, Timothy A. Fields, Yehia Daaka, and Patrick J. Casey. “A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion.J Biol Chem 281, no. 36 (September 8, 2006): 26483–90. https://doi.org/10.1074/jbc.M604376200.
Kelly P, Stemmle LN, Madden JF, Fields TA, Daaka Y, Casey PJ. A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion. J Biol Chem. 2006 Sep 8;281(36):26483–90.
Kelly, Patrick, et al. “A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion.J Biol Chem, vol. 281, no. 36, Sept. 2006, pp. 26483–90. Pubmed, doi:10.1074/jbc.M604376200.
Kelly P, Stemmle LN, Madden JF, Fields TA, Daaka Y, Casey PJ. A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion. J Biol Chem. 2006 Sep 8;281(36):26483–26490.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

September 8, 2006

Volume

281

Issue

36

Start / End Page

26483 / 26490

Location

United States

Related Subject Headings

  • Second Messenger Systems
  • Rho Guanine Nucleotide Exchange Factors
  • Recombinant Fusion Proteins
  • Receptors, G-Protein-Coupled
  • Random Allocation
  • Prostatic Neoplasms
  • Prostate
  • Neoplasm Invasiveness
  • Male
  • Humans