COEXPRESSION AND CROSS-REGULATION OF THE PROLACTIN RECEPTOR AND SEX STEROID-HORMONE RECEPTORS IN BREAST-CANCER

The sex steroid hormones and PRL interact synergistically to control t he neoplastic growth of the mammary gland. The basis for this hormonal synergy is unknown, but may involve cellular coexpression of the sex steroid and PRL receptors, coupled with receptor cross-regulation. To examine this hypothesis the expression of the sex steroid and PRL rece ptors was examined in 20 human breast cancer cell lines and 123 primar y breast cancers. Regulation of sex steroid receptors by PRL and of th e PRL receptor by sex steroids was examined in T-47D and MCF-7 breast cancer cells. Northern analysis of the breast cancer cell lines and tu mors indicated that the PRL receptor and the sex steroid receptors wer e coexpressed. The level of PRL receptor expression in the breast canc er cell lines was linearly related to that of the estrogen and progest erone receptors, but not to that of the androgen receptor. In MCF-7 an d T-47D cells, acute treatment with progestins and androgens and long term treatment with estrogens increased PRL receptor levels. Analysis of sex steroid receptor messenger ribonucleic acid and binding activit y showed that acute PRL treatment produced a time-and concentration-de pendent increase in progesterone receptor and a decrease in androgen r eceptor. These results indicate that receptors for sex steroids and PR L are coexpressed and are cross-regulated, providing a potential mecha nism for the observed synergy among estrogen, progesterone, and PRL in the control of tumor growth.