CANCER G Proteins, New Targets for Prostate Cancer

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 ß 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 Gß 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 Gß signaling to inhibit prostate tumor formation and growth. J. Biol. Chem. 278, 37569-37573 (2003). [Abstract] [Full Text]

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VIRTUAL JOURNAL
Targeting G Signaling to Inhibit Prostate Tumor Formation and Growth

Angela L. Bookout, Amanda E. Finney, Rishu Guo, Karsten Peppel, Walter J. Koch, and Yehia Daaka (26 September 2003)
J. Biol. Chem. 278 (39), 37569. [DOI: 10.1074/jbc.M306276200]
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