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Aromatase Expression in Women’s Cancers

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Book cover Innovative Endocrinology of Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 630))

Abstract

Estrogen has been positively linked to the pathogenesis and growth of three common women’s cancers (breast, endometrium and ovary). A single gene encodes the key enzyme for estrogen biosynthesis named aromatase, inhibition of which effectively eliminates estrogen production in the entire body. Aromatase inhibitors successfully treat breast cancer, whereas their roles in endometrial and ovarian cancers are less clear. Ovary, testis, adipose tissue, skin, hypothalamus and placenta express aromatase normally, whereas breast, endometrial and ovarian cancers overexpress aromatase and produce local estrogen exerting paracrine and intracrine effects. Tissue specific promoters distributed over a 93 kilobase regulatory region upstream of a common coding region alternatively control aromatase expression. A distinct set of transcription factors regulates each promoter in a signaling pathway-and tissue-specific manner. In cancers of breast, endometrium and ovary, aromatase expression is primarly regulated by increased activity of the proximally located promoter I.3/II region. Promoters I.3 and II lie 215 bp from each other and are coordinately stimulated by PGE2 via a cAMP-PKA-dependent pathway. In breast adipose fibroblasts exposed to PGE2 secreted by malignant epithelial cells, activation of PKC potentiates cAMP-PKA-dependent induction of aromatase. Thus, inflammatory substances such as PGE2 may play important roles in inducing local production of estrogen that promotes tumor growth.

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Authors and Affiliations

  1. Department of Obstetric and Gynecology, Northwestern University, 303 E. Superior Street, Suite 4-123, Chicago, IL, 60611, USA

    Serdar E. Bulun

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  1. Serdar E. Bulun
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  2. Evan R. Simpson
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Correspondence to Serdar E. Bulun .

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Editors and Affiliations

  1. Laboratory of Oncoendocrinology, Professor N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia

    Lev M. Berstein MD, PhD, DMS

  2. Division of Endocrinology and Metabolism, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA

    Richard J. Santen MD

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© 2008 Landes Bioscience and Springer Science+Business Media

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Bulun, S.E., Simpson, E.R. (2008). Aromatase Expression in Women’s Cancers. In: Berstein, L.M., Santen, R.J. (eds) Innovative Endocrinology of Cancer. Advances in Experimental Medicine and Biology, vol 630. Springer, New York, NY. https://doi.org/10.1007/978-0-387-78818-0_8

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