Mechanisms enforcing the estrogen receptor β selectivity of botanical estrogens

Yan Jiang, Ping Gong, Zeynep Madak-Erdogan, Teresa Martin, Muthu Jeyakumar, Kathryn Carlson, Ikhlas Khan, Troy J. Smillie, Amar G. Chittiboyina, Sateesh C.K. Rotte, William G. Helferich, John A. Katzenellenbogen, Benita S. Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

Because little is known about the actions of botanical estrogens (BEs), widely consumed by menopausal women, we investigated the mechanistic and cellular activities of some major BEs. We examined the interactions of genistein, daidzein, equol, and liquiritigenin with estrogen receptors ERa and ERβ, with key coregulators (SRC3 and RIP140) and chromatin binding sites, and the regulation of gene expression and proliferation in MCF-7 breast cancer cells containing ERa and/or ERβ. Unlike the endogenous estrogen, estradiol (E2), BEs preferentially bind to ERβ, but their ERβ-potency selectivity in gene stimulation (340- to 830-fold vs. E2) is enhanced at several levels (coregulator recruitment, chromatin binding); nevertheless, at high (0.1 or 1 μM) concentrations, BEs also fully activate ERa. Because ERa drives breast cancer cell proliferation and ERβ dampens this, the relative levels of these two ERs in target cells and the BE dose greatly affect gene expression and proliferative response and will be crucial determinants of the potential benefits vs. risks of BEs. Our findings reveal key and novel mechanistic differences in the estrogenic activities of BEs vs. E2, with BEs displaying patterns of activity distinctly different from those seen with E2 and provide valuable information to inform future studies.

Original languageEnglish (US)
Pages (from-to)4406-4418
Number of pages13
JournalFASEB Journal
Volume27
Issue number11
DOIs
StatePublished - Nov 1 2013

Keywords

  • Breast cancer cells
  • Chromatin binding
  • Gene regulation
  • Proliferation

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Jiang, Y., Gong, P., Madak-Erdogan, Z., Martin, T., Jeyakumar, M., Carlson, K., Khan, I., Smillie, T. J., Chittiboyina, A. G., Rotte, S. C. K., Helferich, W. G., Katzenellenbogen, J. A., & Katzenellenbogen, B. S. (2013). Mechanisms enforcing the estrogen receptor β selectivity of botanical estrogens. FASEB Journal, 27(11), 4406-4418. https://doi.org/10.1096/fj.13-234617