G Proteins, New Targets for Prostate Cancer

Science's STKE  30 Sep 2003:
Vol. 2003, Issue 202, pp. TW378
DOI: 10.1126/stke.2003.202.TW378


Prostate cancer typically starts as an androgen-dependent tumor, but then can progress to androgen independence. Bookout et al. investigated the role of heterotrimeric guanine nucleotide binding proteins (G proteins), specifically the βγ subunit, in androgen-independent tumor growth in culture and in vivo. Androgen-independent PC3 human prostate cancer cells exhibited increased apoptosis when treated with recombinant adenovirus to induce expression of a Gβγ inhibitor, a peptide from the C terminus of G protein-coupled receptor (GPCR) kinase 2 (GRK2ct). PC3 cells expressing the GRK2ct showed slower tumor formation when injected into athymic male mice. Furthermore, injection of adenovirus carrying GRK2ct into preformed tumor slowed tumor growth and promoted apoptosis in the region adjacent to the injection site. Thus, inhibition of G protein signaling may represent another strategy for treatment of androgen-independent prostate cancer.

A. L. Bookout, A. E. Finney, R. Guo, K. Peppel, W. J. Koch, Y. Daaka, Targeting Gβγ signaling to inhibit prostate tumor formation and growth. J. Biol. Chem. 278, 37569-37573 (2003). [Abstract] [Full Text]