Increased expression of cytochrome P450 1A1 and 1B1 genes in anti-estrogen-resistant human breast cancer cell lines

The expression of CYP1A1 and CYP1B1,encoding enzymes known to play a centra l role in oxidative metabolism of a wide range of compounds including stero ids, was significantly increased in anti-estrogen-resistant human breast ca ncer cell lines. This was a purely regulatory phenomenon because no gene am plification had occurred. In anti-estrogen-sensitive MCF-7 cells, the stero idal anti-estrogen, ICI 182780, is able to induce the expression of the ary lhydrocarbon receptor (AhR)-regulated gene product, CYP1A1, via an estrogen receptor (ER)- mediated process. This observation suggests cross-talk betw een the AhR and ER systems. Surprisingly, the increased constitutive expres sion in anti-estrogen-resistant cells of CYP1A1 and CYP1B1 mRNAs, encoding detoxification enzymes, had no effect on the activity of the ICI 182780 com pound. The ICI 182780 regulation of estradiol-inducible genes was found to be identical in the resistant and sensitive breast cancer cell lines. In co nclusion, anti-estrogen resistance is not due to conversion of ICI 182780 t o less active compounds. Int. J. Cancer 88:902-906, 2000. (C) 2000 Wiley-Li ss, Inc.