GROWTH OF LNCAP HUMAN PROSTATE-CANCER CELLS IS STIMULATED BY ESTRADIOL VIA ITS OWN RECEPTOR

We report that growth of LNCaP human prostate cancer cells is signific antly stimulated (up to 120% above control) by physiological estradiol (E(2)) concentrations. This growth increase appears to be comparable to that induced by either testosterone or dihydrotestosterone, as also reported by others. This paper presents novel illustrative evidence f or estrogen-binding proteins and messenger RNA transcripts in LNCaP ce lls. In fact, 1) the reverse transcriptase-polymerase chain reaction s ystem documented normal messenger RNA for estrogen receptors (ER); 2) the radioligand binding assay allowed the detection of high affinity, reduced capacity binding sites in both soluble and nuclear cell fracti ons; and 3) the immunocytochemical analysis showed a consistently inte nsive staining for both ER and progesterone receptors. Compared to oth er human estrogen-responsive mammary cancer cells, MCF7 and ZR75-1, ER expression in LNCaP cells was not significantly lower, as shown by le vels of the ER transcripts, number of sites per cell, or femtomoles pe r mg DNA as well as the percentage and intensity of immunocytochemical staining. A relative estimate of ER expression obtained by matching L NCaP with another human prostate cancer cell line, PC3, always display ed significantly and consistently higher levels in LNCaP cells. The de tection of relatively high type I ER content in either cell compartmen t of LNCaP cells was paralleled by a highly intensive staining for pro gesterone receptors. In addition, evidence that the synthetic androgen R1881 did not compete for type I binding of E(2) and that any E(2)-in duced growth was completely reversed by the pure antiestrogen ICI-182, 780, but unaffected by the antiandrogen Casodex, clearly suggests that the biological response of LNCaP cells to E(2) is mediated via its ow n receptor.