GROWTH-INHIBITORY RESPONSE TO ACTIVIN-A AND ACTIVIN-B BY HUMAN PROSTATE TUMOR-CELL LINES, LNCAP AND DU145

Activins are growth and differentiation factors which have been shown to have proliferative and antiproliferative actions in many tissues. I n addition, they have been implicated in tumourigenesis in reproductiv e tissues. Although activin and inhibin are present in rat ventral pro state, inhibin beta, but not alpha, subunit proteins have been detecte d in the human prostate epithelial tumour cell lines LNCaP, DU145 and PC3. With this absence of capacity to produce inhibins, the aims of th is study were to determine the effect of activin A and B and follistat in on DNA synthesis by these human prostate tumour cell lines. The res ults demonstrate a differential response to exogenously added activin A and B on DNA synthesis in vitro by the tumour cell Lines. The inhibi tory effects were observed on LNCaP cells in the absence or presence o f stimulation with 1 nM 5 alpha-dihydrotestosterone and on the androge n-independent DU145 cells, but not the PC3 cells. Activin A caused a d ose-dependent inhibition of DNA synthesis and proliferation by LNCaP a nd androgen-independent DU145 cells which was maximal at 8 ng/ml. The effect of exogenously added activin A was completely reversed by folli statin, but not by inhibin A. The addition of human recombinant FS 288 alone (400 ng/ml) did not have any effect on DNA synthesis, whereas i nhibin A alone (400 ng/ml) caused a significant inhibition of DNA synt hesis. The capacity of all three cell lines to produce activins and fo llistatins was demonstrated by the expression of the mRNAs and confirm ed by the localisation of immunoreactivity for these ligands to the cy toplasm of the tumour cells. The growth inhibitory response to activin s A and B by LNCaP and DU145 cells, and the ability of follistatin to block these effects, suggest that the autocrine interactions between a ctivins and follistatins have a role in the regulation of LNCaP and DU 145 prostate tumour cell growth.