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Estrogen receptors (ERs) mediate most of the biological effects of estrogen in mammary and uterine epithelial cells by binding to estrogen response elements in the promoter region of target genes or through protein-protein interactions. Anti-estrogens such as tamoxifen inhibit the growth of ER-positive breast cancers by reducing the expression of(More)
Crosstalk between the oestrogen receptor (ER) and ERBB2/HER-2 pathways has long been implicated in breast cancer aetiology and drug response, yet no direct connection at a transcriptional level has been shown. Here we show that oestrogen-ER and tamoxifen-ER complexes directly repress ERBB2 transcription by means of a cis-regulatory element within the ERBB2(More)
The mechanisms involved in resistance to estrogen deprivation are of major importance for optimal patient therapy and the development of new drugs. Long term culture of MCF-7 cells in estrogen (E2)-depleted medium (long term estrogen deprivation; LTED) results in hypersensitivity to E2 coinciding with elevated levels of estrogen receptor (ER) alpha(More)
Deaths from breast cancer have fallen markedly over the past decade due, in part, to the use of endocrine agents that reduce the levels of circulating oestrogens or compete with oestrogen for binding to its receptor. However, many breast tumours either fail to respond or become resistant to endocrine therapies. By understanding the mechanisms that underlie(More)
Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. More than 100 internationally recognised specialist breast cancer scientists, clinicians and(More)
PURPOSE Trichostatin A (TSA), an antifungal antibiotic with cytostatic and differentiating properties in mammalian cell culture, is a potent and specific inhibitor of histone deacetylase (HDAC) activity. The purpose of this study was to evaluate the antiproliferative and HDAC inhibitory activity of TSA in vitro in human breast cancer cell lines and to(More)
Phosphorylation of the estrogen receptor alpha (ERalpha) N-terminal transcription activation function AF1 at serine 118 (S118) modulates its activity. We show here that human ERalpha is phosphorylated by the TFIIH cyclin-dependent kinase in a ligand-dependent manner. Furthermore, the efficient phosphorylation of S118 requires a ligand-regulated interaction(More)
Oestrogen receptor-alpha (ERalpha) is an important prognostic marker in breast cancer and endocrine therapies are designed to inhibit or prevent ERalpha activity. In vitro studies have indicated that phosphorylation of ERalpha, in particular on serine 118 (S118), can result in activation in a ligand-independent manner, thereby potentially contributing to(More)
The knowledge that steroids play a pivotal role in the development of breast cancer has been exploited clinically by the development of endocrine treatments. These have sought to perturb the steroid hormone environment of the tumour cells, predominately by withdrawal or antagonism of oestrogen. Unfortunately, the beneficial actions of existing endocrine(More)
The androgen receptor (AR) mediates the growth-stimulatory effects of androgens in prostate cancer cells. Identification of androgen-regulated genes in prostate cancer cells is therefore of considerable importance for defining the mechanisms of prostate-cancer development and progression. Although several studies have used microarrays to identify(More)