Importancia de las proteínas G heterotriméricas en la biología molecular del cáncer de próstata

Abstract

ObjectiveTo deep in the knowledge of the involvement of G-protein αs and αi subunits in human prostate cancer. MethodsProstate tissue from 9 patients undergoing radical prostatectomy for prostate cancer and 5 controls undergoing cystoprostatectomy for bladder carcinoma. G-protein αs and αi 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). ResultsAt mRNA level, the expression of αs, αi1, αi2 y αi3 was detected in healthy and cancerous tissues. At protein level, the expression of αs y αi1,2 diminished (25% and 40%, respectively) in prostate cancer. The expression of αi3/0 also diminished, whereas that of ß 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 αs. However, digestion at αi2 level with BstU I enzyme served to observe a change of Gln205 (CAG triplet) to Pro (CCG). ConclusionsThe 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 αi2 that, therefore, is stabilized in its active form.