Endocrine Abstracts

Estrogen receptors (ER) are expressed in the majority of breast cancers, are key drivers of breast cancer development and progression and hence therapies to inhibit their activities are a mainstay of treatment for breast cancer. A large proportion of patients develop resistance to these therapies, so determining the mechanisms of ER action is important for improving patient management and for identifying new therapies. In defining the mechanisms by which ER regulates gene expr...

Oestrogens promote breast cancer development and progression by binding to the oestrogen receptors. Oestrogen receptor-alpha (ER) is a transcription regulatory protein that is activated upon binding oestrogen and acts by controlling gene expression in breast cancer cells and is the target for endocrine therapies that inhibit its activity by competing with oestrogen for binding to ER (anti-oestrogens) or by inhibiting oestrogen biosynthesis (aromatase inhibitors). These therapi...

Prostate cancer is currently treated with hormonal therapies, which aim to block the production and/or action of androgens. However, tumours eventually progress to castration-resistant prostate cancer and there is a great need for new therapeutic approaches. We have designed and tested engineered repressors which could be effective in circumstances where current therapies fail. These consist of two modules: an interaction domain, which binds directly to the androgen receptor (...

Estrogen receptor α (ERα) is a key transcriptional regulator in the majority of breast cancers. ERα-positive patients are frequently treated with tamoxifen, but resistance is common. Through ChIP-seq analyses, we presviously identified direct target genes of ERα acting in complex with SRC1, SRC2 or SRC3 (Zwart et al., 2011 EMBO J). Only the 111 genes there were under direct control of ERα in conjunction with SRC3 (but not the other two p160s) predicted...