MTA1, a transcriptional activator of breast cancer amplified sequence 3

AE Gururaj, RR Singh, SK Rayala, Caroline Wigerup, P den Hollander, H Zhang, S Balasenthil, AH Talukder, Göran Landberg, R Kumar

Research output: Contribution to journalArticlepeer-review

95 Citations (SciVal)

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.
Original languageEnglish
Pages (from-to)6670-6675
JournalProceedings of the National Academy of Sciences
Volume103
Issue number17
DOIs
Publication statusPublished - 2006

Subject classification (UKÄ)

  • Cell and Molecular Biology
  • Cancer and Oncology

Keywords

  • estrogen receptor
  • BCAS3
  • coactivator

Fingerprint

Dive into the research topics of 'MTA1, a transcriptional activator of breast cancer amplified sequence 3'. Together they form a unique fingerprint.

Cite this