Low expression of Ga protein subunits in human prostate cancer

Purpose: Because of increasing interest in G protein regulation of cell gro wth, differentiation and oncogenesis, we studied the functionality and expr ession of different G protein subunits in human prostate adenocarcinoma. Ma terials and Methods: Surgical prostate specimens from control patients with bladder cancer and patients with prostate cancer were used. The functional ity of alphas and alphai G protein subunits was evaluated by studying somat ostatin or guanyl-5'-yl-imidotriphosphate regulation of forskolin stimulate d adenylyl cyclase activity. The expression of alphas, alphai and beta subu nits was studied by reverse transcriptase-polymerase chain reaction and imm unoblot analysis. Results: Adenylyl cyclase sensitivity to somatostatin inhibition decreased in prostate cancer. Low guanyl-5'-yl-imidotriphosphate doses inhibited fors kolin stimulated adenylyl cyclase, whereas the opposite was true at high co ncentrations, evidencing the functionality of ai and as, respectively, in n ormal and cancer tissue samples. Reverse transcriptase-polymerase chain rea ction revealed RNA encoding for as and alpha i1,2,3 subclasses in normal an d pathological conditions. However, immunoblot analysis showed that the lev el of beta subunits was maintained, whereas that of alphas and alphai subun its decreased 30% to 40% after neoplastic transformation. The levels of as and ai1,2 subunits correlated inversely with serum prostate specific antige n in patients with prostate cancer. Conclusions: The functionality and expression of G protein subunits are sel ectively modified in human prostate adenocarcinoma. Low as and ai levels in prostate cancer suggest an important regulatory role of G proteins for cel l proliferation and neoplastic transformation in the human prostate and the y may have prognostic value.