Pas de deux: Chromatin binding of androgen and estrogen receptors in breast cancer — ASN Events

Pas de deux: Chromatin binding of androgen and estrogen receptors in breast cancer (#62)

W. D. Tilley 1 , J. L. L. Robinson 2 , J. S. Carroll 2 , T. E. Hickey 1
  1. Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, Australia
  2. CRUK Cambridge Research Institute, Cambridge University, Cambridge, United Kingdom

Androgen and estrogen receptors are steroid hormone-induced nuclear transcription factors that interact directly or indirectly with chromatin to regulate transcriptional programs within cells during phases of normal growth and differentiation or as part of pathogenic processes, particularly of reproductive endocrine tumours. For example, the androgen receptor (AR) and the estrogen receptor alpha (ERα) are individually considered the major oncogenic drivers of prostate and breast cancer respectively, but these receptors are frequently co-expressed in primary prostate and breast tumours. Our more recent research has focussed on the DNA binding patterns of AR and ERα in different molecular subtypes of breast cancer, with specific focus on patterns of AR binding in the presence or absence of ERα and FOXA1, the latter a major determinant (“pioneer factor”) that dictates where AR and ERα binds to chromatin within a genome. These studies are beginning to elucidate the molecular mechanisms whereby the AR exerts tumour suppressive or oncogenic actions within breast cancer cells. Targeting the AR for treatment of breast cancer is currently being explored, with several clinical trials underway in the USA and UK. In particular, this therapeutic strategy is expected to expand options for women with breast cancers that are ineligible for treatment with tamoxifen or aromatase inhibitors. Since the influence of AR signalling in breast cancer cells displays plasticity dependent on context, our goal is to develop robust markers of AR action to facilitate patient selection for currently available AR target therapies and pave the way for development of novel agents or selective AR modulators as a new wave in breast cancer therapeutics.

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