ESTRADIOL INHIBITS GROWTH OF HORMONE-NONRESPONSIVE PC3 HUMAN PROSTATE-CANCER CELLS

Significant inhibition of proliferative activity in PC3 human prostate cancer cells by estradiol is reported, accompanied by experimental ev idence for a specific estrogen receptor (ER). Radioligand-binding assa ys revealed the presence of high affinity sites of estrogen binding in the nuclear compartment of PC3 cells. In addition, using a reverse tr anscriptase-polymerase chain reaction system, we obtained evidence of either normal or a variant ER mRNA; the latter, which lacks the entire exon 4, is coexpressed with normal ER mRNA and has been recently char acterized in our laboratories. The likelihood that the inhibitory effe ct erected by estradiol could be mediated by an increase of transformi ng growth factor beta (TGF beta) production was also investigated. Use of monoclonal antibodies against TGF beta(1) produced a 3-fold increa se of growth rate in PC3 cells; this clearly speaks for high levels of endogenous TGF beta(1). This effect was almost completely abolished a fter addition of 100 nM estradiol. However, we failed to demonstrate a ny increase of TGF beta(1) mRNA after estradiol administration using N orthern blot analysis. Further studies are needed to ascertain whether the estradiol-induced growth inhibition of PC3 cells is either mediat ed by other TGF beta species or exerted via alternative mechanism(s).