Low expression of Ga protein subunits in human prostate cancer

Purpose: Because of increasing interest in G protein regulation of cell growth, differentiation and oncogenesis, we studied the functionality and expression of different G protein subunits in human prostate adenocarcinoma. Materials and Methods: Surgical prostate specimens from control patients with bladder cancer and patients with prostate cancer were used. The functionality of alphas and alphai G protein subunits was evaluated by studying somatostatin or guanyl-5'-yl-imidotriphosphate regulation of forskolin stimulated adenylyl cyclase activity. The expression of alphas, alphai and beta subunits was studied by reverse transcriptase-polymerase chain reaction and immunoblot analysis. Results: Adenylyl cyclase sensitivity to somatostatin inhibition decreased in prostate cancer. Low guanyl-5'-yl-imidotriphosphate doses inhibited forskolin stimulated adenylyl cyclase, whereas the opposite was true at high concentrations, evidencing the functionality of ai and as, respectively, in normal and cancer tissue samples. Reverse transcriptase-polymerase chain reaction revealed RNA encoding for as and alpha i1,2,3 subclasses in normal and pathological conditions. However, immunoblot analysis showed that the level of beta subunits was maintained, whereas that of alphas and alphai subunits decreased 30% to 40% after neoplastic transformation. The levels of as and ai1,2 subunits correlated inversely with serum prostate specific antigen in patients with prostate cancer. Conclusions: The functionality and expression of G protein subunits are selectively modified in human prostate adenocarcinoma. Low as and ai levels in prostate cancer suggest an important regulatory role of G proteins for cell proliferation and neoplastic transformation in the human prostate and they may have prognostic value.