MTA1, a transcriptional activator of breast cancer amplified sequence 3

Anupama E. Gururaj, Rajesh R. Singh, Suresh K. Rayala, Caroline Holm, Petra Den Hollander, Hao Zhang, Seetharaman Balasenthil, Amjad H. Talukder, Goran Landberg, Rakesh Kumar

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Here we define a function of metastasis-associated protein 1 (MTA1), a presumed corepressor of estrogen receptor α(ERα), as a transcriptional activator of Breast Cancer Amplified Sequence 3 (BCAS3), a gene amplified and overexpressed in breast cancers. We identified BCAS3 as a MTA1 chromatin target in a functional genomic screen. MTA1 stimulation of BCAS3 transcription required ERα and involved a functional ERE half-site in BCAS3. Furthermore, we discovered that MTA1 is acetylated on lysine 626, and that this acetylation is necessary for a productive transcriptional recruitment of RNA polymerase II complex to the BCAS3 enhancer sequence. BCAS3 expression was elevated in mammary tumors from MTA1 transgenic mice and 60% of the human breast tumors, and correlated with the coexpression of MTA1 as well as with tumor grade and proliferation of primary breast tumor samples. These findings reveal a previously unrecognized function of MTA1 in stimulating BCAS3 expression and suggest an important role for MTA1-BCAS3 pathway in promoting cancerous phenotypes in breast tumor cells. © 2006 by the National Academy of Sciences of the USA.
    Original languageEnglish
    Pages (from-to)6670-6675
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume103
    Issue number17
    DOIs
    Publication statusPublished - 25 Apr 2006

    Keywords

    • BCAS3
    • Coactivator
    • Estrogen receptor

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