Abstract
Members of the nuclear receptor superfamily are ligand-regulated transcription factors involved in the control of a broad range of normal physiological and disease processes. The estrogen receptor alpha (ERα) is a member of the steriod receptor family, which is part of the nuclear receptor superfamily. ERα it is important for many biological processes and plays a key role in the pathogenesis of breast cancer. Gene regulation by ERα requires the recruitment of a multitude of transcriptional co-regulators to the promoters of estrogen-responsive genes. There is evidence in support of the involvement of these co-regulators in breast cancer progression. We review the role of steroid receptor co-activator-3 (SRC-3), which is frequently amplified in breast cancer, and its role in breast cancer risk, outcome and response to endocrine therapy in patients with breast cancer.
Key Points
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SRC-3/AIB1 is a phosphoprotein and is phosphorylated by estrogen as well as a number of kinases including ERK1/2JNK, p38, IKK α and Abl kinase
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The function of the polyglutamate repeat within SRC-3 is unclear with regard to its possible role as a modifier of breast cancer risk in BRCA1 and BRCA2 carriers
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SRC-3 is critical for somatic growth and normal mammary gland development and its overexpression results in mammary hyperplasia and breast cancer, as well as tumors in other organs
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SRC-3 has been shown to modulate invasion both in both ER positive and ER negative cell lines, its expression in ER negative breast cancer is associated with a poor outcome
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Expression of SRC-3 and its co-expression with members of the EGFR family in breast cancer is associated with a poor outcome in response to tamoxifen therapy
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Further work is required to delineate the precise role of SRC-3 and its potential diagnostic and prognostic potential, as well as its value as a possible therapeutic target
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Acknowledgements
C. Palmieri and C. R. Coombes wish to acknowledge the grant support from Cancer Reasearch UK. The research of O. Gojis is in part funded by a grant from the Ministry of Education of the Czech Republic (Project “Oncology” MSM 0021620808) and is also a recipient of the Translational Research Fellowship from the European Society of Medical Oncology. The Department of Oncology at Imperial College London/Imperial College HealthCare NHS Trust is an Experimental Cancer Medicine Centre (ECMC), which is supported by funds from Cancer Research UK and the Department of Health.
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Gojis, O., Rudraraju, B., Gudi, M. et al. The role of SRC-3 in human breast cancer. Nat Rev Clin Oncol 7, 83–89 (2010). https://doi.org/10.1038/nrclinonc.2009.219
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DOI: https://doi.org/10.1038/nrclinonc.2009.219
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