MTA1, a transcriptional activator of breast cancer amplified sequence 3

Research output: Contribution to journalArticle

Abstract

Here we define a function of metastasis-associated protein 1 (MTA1), a presumed corepressor of estrogen receptor alpha (ER alpha), 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 ERa 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 11 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.

Details

Authors
  • AE Gururaj
  • RR Singh
  • SK Rayala
  • Caroline Wigerup
  • P den Hollander
  • H Zhang
  • S Balasenthil
  • AH Talukder
  • Göran Landberg
  • R Kumar
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
  • Cancer and Oncology

Keywords

  • estrogen receptor, BCAS3, coactivator
Original languageEnglish
Pages (from-to)6670-6675
JournalProceedings of the National Academy of Sciences
Volume103
Issue number17
Publication statusPublished - 2006
Publication categoryResearch
Peer-reviewedYes