The nuclear oxysterol receptor LXRα is expressed in the normal human breast and in breast cancer

The liver X≥receptor α (LXRα) is a nuclear receptor with a key role in bile acid biosynthesis and cholesterol metabolism. The present study investigated the expression and function of LXRα in the normal and malignant human breast. LXRα mRNA transcripts were detected by RT-PCR in nine breast carcinoma cell lines. The nucleotide sequence of the cloned PCR product was identical to the corresponding human LXRα cDNA sequence. Expression of LXRα protein was confirmed by immunoblot analysis of breast cancer cell lysates. LXRα mRNA was expressed in 14/15 (93%) of normal human breast mammoplasty specimens and in 11/15 (73%) of primary breast carcinomas. Oxysterol and nonsteroidal LXRα agonists at low micromolar concentrations inhibited proliferation of breast carcinoma cell lines in culture. The importance of LXRα signaling in cholesterol homeostasis and the observed expression of LXRα in normal breast tissue suggest that this nuclear oxysterol receptor has an important physiological function in the breast. LXRα gene expression is regulated by dietary fatty acids implicated in breast carcinogenesis and detection of LXRα expression in breast cancer cell lines and breast tumors in the present study indicates that LXRα may also be important in breast carcinogenesis. Inhibition of breast cancer cell proliferation suggests that pharmacological LXRα agonists may have potential preventive and/or therapeutic antitumor activity in breast cancer.