MTA1, a transcriptional activator of breast cancer amplified sequence 3

Summary, in English

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.

• Author: AE Gururaj; RR Singh; SK Rayala; Caroline Wigerup; P den Hollander; H Zhang; S Balasenthil; AH Talukder; Göran Landberg; R Kumar
• Department/s: Pathology, Malmö
• Publishing year: 2006
• Language: English
• Pages: 6670-6675
• Publication/Series: Proceedings of the National Academy of Sciences
• Volume: 103
• Issue: 17
• Links: http://dx.doi.org/10.1073/pnas.0601989103
• Document type: Journal article
• Publisher: National Academy of Sciences
• Topic: Cell and Molecular Biology; Cancer and Oncology
• Keywords: estrogen receptor; BCAS3; coactivator
• Status: Published
• Research group: Pathology, Malmö
• ISBN/ISSN/Other: ISSN: 1091-6490