Retinol conversion to retinoic acid is impaired in breast cancer cell lines relative to normal cells

The bioactivity of retinol (vitamin A) is in part dependent on its metaboli sm to retinoic acid (RA), We investigated the ability of breast epithelial cells to synthesize RA when challenged with a physiological retinol dose (2 mu M). Normal human mammary epithelial cells (HMEC) cultured from reductio n mammoplasties were competent in RA synthesis and the ability to synthesiz e RA was retained by immortal, nontumorigenic breast epithelial cell lines (MTSV1.7, MCF-10F, and 184B5). In contrast, most (five of six) breast cance r cell lines could not synthesize RA or did so at low rates relative to nor mal cells. A notable exception was the MDA-MB-468 cell line, which was full y competent in RA synthesis. Most (greater than or equal to 68%) of the RA synthesized by breast cells was recovered from the culture medium. Cellular retinol binding protein and cellular RA binding protein II, both expressed in HMEC, had various expression patterns in the cell lines that did not co rrelate with the observed differences in RA synthesizing ability. Strong RA induction of the RA hydroxylase P450RAI (CYP26) was confined to ER alpha-p ositive T47D and MCF-7 breast cancer cells and did not appear to explain th e lack of detectable RA levels in these cells since RA remained undetectabl e when the cells were treated with 5-10 mu M liarozole, a P450RAI inhibitor . We hypothesize that retinol bioactivity is impaired in breast cancer cell s that cannot synthesize RA. In preliminary support of this hypothesis, we found that retinol (0.5-2 mu M) inhibited MCF-10F but not T47D or MCF-7 cel l growth. (C) 2000 Wiley-Liss, Inc.