Transcriptional control of local estrogen formation by aromatase in the breast

Sarah Quynh Giao To, Kevin Christopher Knower, Vanessa Cheung, Evan Rutherford Simpson, Colin Clyne

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

Abstract

Aromatase is the critical enzyme that converts androgens to estrogens. It is frequently highly expressed in the tumour bearing breast of women diagnosed with estrogen receptor positive tumours, resulting in dramatically increased local estrogen production to drive tumour progression. Expression of aromatase is regulated primarily at the transcriptional level of its encoding gene CYP19A1, located on chromosome 15 of the human genome. A characteristic feature of CYP19A1 expression is its use of alternative promoters to regulate transcription in a tissue-specific manner. In breast cancer, the increase in aromatase expression is mediated via higher expression of the distal adipose-specific promoter I.4 and a switch to the preferential use of proximal promoters I.3 and II. This results in a net increase of CYP19A1 transcripts in tumour-bearing breast up to 3-4-fold higher than normal breast. Current aromatase inhibitors - whilst efficacious - exhibit significant side effects that reduce patient compliance. Understanding the transcription factors and signalling pathways that control aromatase expression will lead to opportunities to develop breast-specific inhibitors with an improved side-effects profile. This article is part of a Special Issue entitled Essential role of DHEA .
Original languageEnglish
Pages (from-to)179 - 186
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume145
DOIs
Publication statusPublished - 2015

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