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Nongenomic Actions of Estrogens and Xenoestrogens Affecting Endocrine Cancer Cells

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Advances in Rapid Sex-Steroid Action

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Abstract

Estrogens act via multiple membrane-associated receptors (α, β, and GPR30) to mediate diverse rapid signaling cascades affecting functional endpoints in both normal and cancer cells. The mitogen-activated protein kinases are a summative signaling node that integrates upstream signaling cascades into responses for major functional cellular outcomes such as proliferation, migration, differentiation, and death. These responses are complex; they oscillate with time, as well as fluctuate up and down with increasing ligand concentration (hormesis). Nonphysiologic estrogenic compounds also use these receptors and signaling systems, but do so imperfectly, causing disruptions to both the phasing and dose-responsiveness of physiologic estrogens. Disruptions to the signaling of different physiologic estrogens could cause life stage-specific tissue malfunctions or cancer vulnerabilities.

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Abbreviations

BPA:

bisphenol A

Ca++:

calcium

E1:

estrone

E2:

estradiol

E3:

estriol

ER:

estrogen receptor

ERK:

extracellular regulated kinase

JUNK:

Jun-kinase

MAPK:

mitogen-activated protein kinase

mERs:

membrane estrogen receptors

mERα:

membrane ERα

NHANES:

National Health and Nutrition Examination Survey

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Acknowledgments

We acknowledge the following funding sources over the last decade for support of our work discussed here: DOD Breast Cancer Initiative (DAMD17-01-1-0418); NIH (ES010987, ES015292, ES006676); American Institute for Cancer Research (06A126); NIH training grants (T32 ES07254, T32 DA07287); the UTMB Center for Addiction Research; the UTMB Sealy Memorial Endowment Fund; and the UTMB Clinical and Translational Science Award UL1RR029876.

Permissions to use previously published materials: We have used two figure panels from previously published work [12] and we authorize its use here according to the rules set forth by BioMed Central on its Web Site. BMC articles are licensed by their respective authors for use and distribution subject to citation of the original source in accordance with the Open Access license.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, 77555, USA

    Cheryl S. Watson, Dragoslava Zivadinovic, Yow-Jiun Jeng, Rebecca A. Alyea & Anannya Banga

  2. Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, 77555, USA

    Terumi Midoro-Horiuti & Randall Goldblum

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  1. Cheryl S. Watson
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  2. Dragoslava Zivadinovic
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  3. Yow-Jiun Jeng
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  4. Rebecca A. Alyea
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  5. Terumi Midoro-Horiuti
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Correspondence to Cheryl S. Watson .

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Editors and Affiliations

  1. University of Naples, Naples, 80138, Italy

    Gabriella Castoria

  2. Department of Pathology, II University of Naples, Naples, 80138, Italy

    Antimo Migliaccio

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Watson, C.S. et al. (2012). Nongenomic Actions of Estrogens and Xenoestrogens Affecting Endocrine Cancer Cells. In: Castoria, G., Migliaccio, A. (eds) Advances in Rapid Sex-Steroid Action. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1764-4_8

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