BCAS2 Enhances carcinogenic effects of estrogen receptor alpha in breast cancer cells

Ángel Salmerón-Hernández, María Yamilet Noriega-Reyes, Albert Jordan, Noemi Baranda-Avila, Elizabeth Langley

    Research output: Contribution to journalArticle

    1 Scopus citations

    Abstract

    Estrogen receptor alpha (ERα) has an established role in breast cancer biology. Transcriptional activation by ERα is a multistep process modulated by coactivator and corepressor proteins. Breast Cancer Amplified Sequence 2 (BCAS2), is a poorly studied ERα coactivator. In this work, we characterize some of the mechanisms through which this protein increases ERα activity and how this promotes carcinogenic processes in breast cancer cells. Using protein-protein interaction and luciferase assays we show that BCAS2 interacts with ERα both in vitro and in vivo and upregulates transcriptional activation of ERα directly through its N-terminal region (AF-1) and indirectly through its C-terminal (AF-2) region, acting in concert with AF-2 interacting coactivators. Elevated expression of BCAS2 positively affects proliferation, clonogenicity and migration of breast cancer cells and directly activates ERα regulated genes which have been shown to play a role in tumor growth and progression. Finally, we used signal transduction pathway inhibitors to elucidate how BCAS2 is regulated in these cells and observed that BCAS2 is preferentially regulated by the PI3K/AKT signaling pathway. BCAS2 is an AF-1 coactivator of ERα whose overexpression promotes carcinogenic processes, suggesting an important role in the development of estrogen-receptor positive breast cancer.

    Original languageEnglish (US)
    Article number966
    JournalInternational journal of molecular sciences
    Volume20
    Issue number4
    DOIs
    StatePublished - Feb 2 2019

    Keywords

    • BCAS2
    • Breast cancer
    • Coactivators
    • Estrogen receptor

    ASJC Scopus subject areas

    • Catalysis
    • Molecular Biology
    • Spectroscopy
    • Computer Science Applications
    • Physical and Theoretical Chemistry
    • Organic Chemistry
    • Inorganic Chemistry

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  • Cite this

    Salmerón-Hernández, Á., Noriega-Reyes, M. Y., Jordan, A., Baranda-Avila, N., & Langley, E. (2019). BCAS2 Enhances carcinogenic effects of estrogen receptor alpha in breast cancer cells. International journal of molecular sciences, 20(4), [966]. https://doi.org/10.3390/ijms20040966