Characterization of Estrogen and Progesterone Receptors and the Dissociated Regulation of Growth and Progesterone Receptor Stimulation by Estrogen in MDA–MB–134 Human Breast Cancer Cells

Georg C.A. Reiner, Benita S. Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

We have examined the properties of the estrogen receptor and progesterone receptor in MDA–MB–134 human breast cells and have evaluated the effects of estrogen on cell proliferation and progesterone receptor levels in these cells as indices of hormonal sensitivity. These cells contain high levels of estrogen receptor (approximately 1.5 pmol/mg DNA) and low levels of progesterone receptor (0.15 pmol/mg DNA). More than 80% of the estrogen receptor is found in the nuclear fraction in the absence of estrogen, and the Kd of the receptor for estradiol is approximately 1.5 x 10-10m. Upon exposure to estradiol, the receptors become occupied, but there is no processing or apparent decrease in either nuclear or total cellular estrogen receptor content, as can be seen in MCF-7 human breast cancer cells. The nuclear estrogen receptor sediments as a 4.6S species on high salt sucrose gradients, and it can be detected on sodium dodecyl sulfate-polyacrylamide gel immunoblot analysis as a species of molecular weight 65,000, identical to that of the MCF-7 estrogen receptor, using the monoclonal antibodies D75P3γ and H222Spγ prepared against the MCF-7 estrogen receptor. The estrogen receptor shows binding selectivity for estrogens and antiestrogens, and its affinity for ligands follows the order diethylstilbestrol (190%) estradiol (100%) estriol (13%) tamoxifen (3%), as expected for estrogen receptor. Hence the receptor appears normal in many of its physicochemical properties and in terms of its binding affinity and specificity for estrogens and antiestrogens. Control cells contain low levels of progesterone receptor that display high affinity (Kd = 6 x 10-9m) for the synthetic progestin R5020, but exposure to estradiol (10-11-10-7m) fails to increase cellular progesterone receptor levels. In contrast, estradiol markedly stimulates the rate of cell proliferation, while tamoxifen suppresses the growth of control and of estradiol treated cells. Hence, our data show that these cells, which contain substantial levels of estrogen receptor, respond to estrogen with enhanced cell proliferation but fail to have their progesterone receptor level modulated by estradiol. These cells represent an interesting and unusual situation in which estrogenic regulation of proliferation and the stimulation of progesterone receptor are dissociated. These cells should prove useful in further evaluation of estrogenic.

Original languageEnglish (US)
Pages (from-to)1124-1131
Number of pages8
JournalCancer Research
Volume46
Issue number3
StatePublished - Mar 1 1986

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Characterization of Estrogen and Progesterone Receptors and the Dissociated Regulation of Growth and Progesterone Receptor Stimulation by Estrogen in MDA–MB–134 Human Breast Cancer Cells'. Together they form a unique fingerprint.

  • Cite this