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The role of SRC-3 in human breast cancer

Nature Reviews Clinical Oncology volume 7, pages 83–89 (2010)Cite this article

A Correction to this article was published on 01 March 2010

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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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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Figure 1: Structural domains and phosphorylation sites of SRC-3.

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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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Authors and Affiliations

  1. Department of Pathology, Third Faculty of Medicine, Charles University Prague, Ruska 87, Prague 10, 10000, Czech Republic

    Ondrej Gojis

  2. Department of Oncology, Cancer Research UK Laboratories, Imperial College London Hammersmith Campus, Du Cane Road, W12 0NN, London, UK

    Ondrej Gojis, Bharath Rudraraju, Charles R. Coombes, Susan Cleator & Carlo Palmieri

  3. Department of Histopathology, Imperial College Healthcare NHS Trust, Fulham Palace Road, W6 8RF, London, UK

    Mihir Gudi & Sami Sousha

  4. Department of Surgery, Imperial College Healthcare NHS Trust, Fulham Palace Road, W6 8RF, London, UK

    Katy Hogben

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Summary of information on the role of the SRC-3 polyglutamate repeat in modifying breast cancer risk. (DOC 189 kb)

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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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