Alterations of expression and regulation of transforming growth factor β in human cancer prostate cell lines

TGFbeta can promote and/or suppress prostate tumor growth through multiple and opposing actions. Alterations of its expression, secretion, regulation or of the sensitivity of target cells can lead to a favorable environment for tumor development. To gain a better insight in TGFbeta function during cancer progression, we have used different cultured human prostate cells: preneoplastic PNT2 cells, the androgen-dependent LNCaP and the androgen-independent PC3 and DU145 prostate cancer cell lines. We have studied by specific ELISA assays in conditioned media (CM), the secretion of TGFbeta1 and TGFbeta2 in basal conditions and after hormonal treatment (DHT or E2) and the expression of TGFbeta1 mRNA by Northern blot. We have also compared the effect of fibroblast CM on TGFbeta secretion by the different cell types. Compared to PNT2 cells, cancer cell lines secrete lower levels of active TGFbeta which are not increased in the presence of fibroblast CM. LNCaP cells respond to androgen or estrogen treatment by a 10-fold increase of active TGFbeta secretion while PC3 and DU145 are unresponsive. In conclusion, prostate cancer cell lines have lost part of their ability to secrete and activate TGFbeta, and to regulate this secretion through stromal-epithelial interactions. Androgen-sensitive cancer cells may compensate this loss by hormonal regulation. (C) 2002 Elsevier Science Ltd. All rights reserved.