[Importance of heterotrimeric G proteins in prostate cancer molecular biology].
OBJECTIVE
To deep in the knowledge of the involvement of G-protein alphas and alphai 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 alphas and alphai 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 alphas, alphai1, alphai2 y alphai3 was detected in healthy and cancerous tissues. At protein level, the expression of alphas y alphai1,2 diminished (25% and 40%, respectively) in prostate cancer. The expression of alphai3/0 also diminished, whereas that of beta 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 alphas. However, digestion at alphai2 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 alphai2 that, therefore, is stabilized in its active form.
Prieto Villapun
J C
JC
Departamento de Bioquímica y Biologia Molecular, Universidad de Alcald, Alcalá de Henares.
Solano Haro
R M
RM
Carmena Sierra
M J
MJ
Sánchez-Chapado
M
M
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011471:Prostatic Neoplasms / Q000235:genetics*
D044385:GTP-Binding Protein alpha Subunits