Abstract

PRIETO VILLAPUN, J.C.; SOLANO HARO, R.M.; CARMENA SIERRA, M.J.  and  SANCHEZ-CHAPADO, M.. Importance of  heterotrimeric G proteins in prostate cancer molecular biology. Actas Urol Esp [online]. 2005, vol.29, n.10, pp.948-954. ISSN 0210-4806.

Objective: To deep in the knowledge of the involvement of G-protein α_s and α_i subunits in human prostate cancer. Methods: Prostate tissue from 9 patients undergoing radical prostatectomy for prostate cancer and 5 controls undergoing cystoprostatectomy for bladder carcinoma. G-protein α_s and α_i subunits were studied for expression (mRNA by RT-PCR and protein by Western-blot), functionality (adenylyl cyclase activity, AC) and possibility of mutations (analysis with restriction enzymes and cDNA sequentiation). Results: At mRNA level, the expression of α_s, α_i1, α_i2 y α_i3 was detected in healthy and cancerous tissues. At protein level, the expression of α_s y α_i1,2 diminished (25% and 40%, respectively) in prostate cancer. The expression of αi3/0 also diminished, whereas that of ί subunit was not modified. Basal AC activity in adenocarcinoma membranes was 40% inferior to the control. Digestion with restriction enzymes Eag I or AlwN I did not allow to locate mutations in α_s. However, digestion at α_i2 level with BstU I enzyme served to observe a change of Gln²⁰⁵ (CAG triplet) to Pro (CCG). Conclusions: The functionality and expression of heterotrimeric G proteins are selectively modified in human prostate adenocarcinoma, occurring in addition some punctual mutation. The observed substitution of Gln²⁰⁵ by Pro may result in a low GTPase activity for α_i2 that, therefore, is stabilized in its active form.

Keywords : Prostate cancer; G proteins; Expression; Mutations.

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