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

✍ Scribed by Peter Coopman; Marcel Garcia; Nils Brünner; Danielle Derocq; Robert Clarke; Henri Rochefort

• Book ID: 102864467
• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: French
• Weight: 868 KB
• Volume: 56
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910560225

✦ Synopsis

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 OHTarn on these 2 rnRNAs. OHTarn was more effective than E2 in increasing cathepsin-D mRNA levels, supporting the idea that anti-estrogen-resistant breast cancer continues to overexpress cathepsin-D. These data show that the steroidal antiestrogens 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.