Differential steroid hormone regulation of human glandular kallikrein (hK2) and prostate-specific antigen (PSA) in breast cancer cell lines

We have investigated the steroid hormone regulation of human glandular kall ikrein (hK2) and prostate-specific antigen (PSA) in the breast cancer cell lines BT-474, T-47D, MFM-223, MCF-7, ZR-75-1, MDA-MB-435, and BT-20. Using highly sensitive time-resolved fluorometric immunoassays, we were able to d etect significant amounts of both kallikreins in tissue culture supernatant s of BT-474, T-47D, and MFM-223 cells after hormonal stimulation. However, BT-474 cells produce much more hK2 than PSA, whereas the situation is rever sed in T-47D cells. Furthermore, BT-474 cells produce, on absolute terms, a bout 500-1,000-fold more hK2 than T-47D cells. From all steroids tested, mi bolerone, a synthetic non-metabolizable androgen, was the most potent stimu lator for both kallikreins followed by the synthetic progestin norgestrel. Estradiol was able to induce production of small but significant amounts of hK2 and PSA in the BT-474 cell line, supporting the notion that there is a cross-talk between the estrogen and androgen hormone-receptor signaling pa thways. MFM-223 is an androgen responsive cell line, devoid of other steroi d hormone receptors, which is also capable of producing hK2 and PSA but at much lower amounts. MCF-7 and ZR-75-1 cell lines failed to produce any prot ein, even though they have similar steroid receptor content as the BT-474 a nd T-47D cell lines. This was also the case for MDA-MB-435, a cell line ric h in androgen receptors. Our data suggest that the expression of the hK2 ge ne in breast cancer cell lines is mainly under the control of androgens and progestins, similarly to PSA. These cell lines may represent good models f or studying the differential expression of these two genes and for identify ing cellular factors (e.g. co-activators/co-repressors), which may modify t he potency of expression after hormonal stimulation.