Increased expression of cytochrome p450 1A1 and 1B1 genes in anti-estrogen-resistant human breast cancer cell lines

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Abstract
The expression of CYP1A1 and CYP1B1, encoding enzymes known to play a central role in oxidative metabolism of a wide range of compounds including steroids, was significantly increased in anti‐estrogen–resistant human breast cancer cell lines. This was a purely regulatory phenomenon because no gene amplification had occurred. In anti‐estrogen–sensitive MCF‐7 cells, the steroidal anti‐estrogen, ICI 182780, is able to induce the expression of the arylhydrocarbon receptor (AhR)‐regulated gene product, CYP1A1, via an estrogen receptor (ER)‐ mediated process. This observation suggests cross‐talk between the AhR and ER systems. Surprisingly, the increased constitutive expression in anti‐estrogen–resistant cells of CYP1A1 and CYP1B1 mRNAs, encoding detoxification enzymes, had no effect on the activity of the ICI 182780 compound. The ICI 182780 regulation of estradiol‐inducible genes was found to be identical in the resistant and sensitive breast cancer cell lines. In conclusion, anti‐estrogen resistance is not due to conversion of ICI 182780 to less active compounds. Int. J. Cancer 88:902–906, 2000.

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