Anti‐proliferative and anti‐estrogenic effects of ICI 164,384 and ICI 182,780 in 4‐OH‐tamoxifen‐resistant human breast‐cancer cells

The effects of the anti‐estrogens 4‐hydroxytamoxifen (OHTam), ICI 164,384 and ICI 182,780 were tested on the MCF‐7/LCC2 breast‐carcinoma cell line, which grows significantly in the presence of OHTam and serves as a model for studying anti‐estrogen resistance of estrogen‐receptor‐positive breast cancer. Cell proliferation and cathepsin‐D secretion were strongly inhibited by either ICI 182,780 or ICI 164,384 alone or ICI 164,384 in combination with 17‐p‐estradiol (E2) or OHTam. ICI 164,384 alone did not affect the cathepsin‐D and pS2 mRNA levels, but antagonized the stimulatory effects of E2 or OHTam on these 2 mRNAs. OHTam was more effective than E2 in increasing cathepsin‐D mRNA levels, supporting the idea that anti‐estrogen‐resistant breast cancer continues to over‐express cathepsin‐D. These data show that the steroidal anti‐estrogens ICI 164,384 and ICI 182,780 retain their ability to inhibit cell proliferation and the estrogen‐responsiveness of cathepsin‐D and pS2 genes in the OHTam‐resistant MCF‐7/ LCC2 cell line. These pure anti‐estrogens may thus be efficient second‐line treatments of some Tamoxifen‐resistant tumors.