Aromatase expression in women's cancers

Serdar E. Bulun*, Evan R. Simpson

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

60 Scopus citations

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.

Original languageEnglish (US)
Title of host publicationInnovative Endocrinology of Cancer
EditorsLev Berstein, Richard Santen
Pages112-132
Number of pages21
DOIs
StatePublished - 2008

Publication series

NameAdvances in Experimental Medicine and Biology
Volume630
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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