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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 the 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 hypothe...

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Published in:The journal of clinical endocrinology and metabolism 1997-11, Vol.82 (11), p.3692-3699
Main Authors: ORMANDY, C. J, HALL, R. E, MANNING, D. L, ROBERTSON, J. F. R, BLAMEY, R. W, KELLY, P. A, NICHOLSON, R. I, SUTHERLAND, R. L
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container_end_page 3699
container_issue 11
container_start_page 3692
container_title The journal of clinical endocrinology and metabolism
container_volume 82
creator ORMANDY, C. J
HALL, R. E
MANNING, D. L
ROBERTSON, J. F. R
BLAMEY, R. W
KELLY, P. A
NICHOLSON, R. I
SUTHERLAND, R. L
description The sex steroid hormones and PRL interact synergistically to control the 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 receptors was examined in 20 human breast cancer cell lines and 123 primary breast cancers. Regulation of sex steroid receptors by PRL and of the 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 tumors indicated that the PRL receptor and the sex steroid receptors were coexpressed. The level of PRL receptor expression in the breast cancer cell lines was linearly related to that of the estrogen and progesterone receptors, but not to that of the androgen receptor. In MCF-7 and 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 activity showed that acute PRL treatment produced a time- and concentration-dependent increase in progesterone receptor and a decrease in androgen receptor. These results indicate that receptors for sex steroids and PRL are coexpressed and are cross-regulated, providing a potential mechanism for the observed synergy among estrogen, progesterone, and PRL in the control of tumor growth.
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source Oxford Journals Online
subjects Biological and medical sciences
Blotting, Northern
Breast Neoplasms - genetics
Dihydrotestosterone - pharmacology
Estradiol - pharmacology
Female
Gene Expression Regulation, Neoplastic - drug effects
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Progesterone - pharmacology
Prolactin - pharmacology
Receptors, Androgen - genetics
Receptors, Estrogen - genetics
Receptors, Progesterone - genetics
Receptors, Prolactin - genetics
Receptors, Steroid - genetics
Tumor Cells, Cultured
Tumors
title Coexpression and cross-regulation of the prolactin receptor and sex steroid hormone receptors in breast cancer
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