MTA1, a transcriptional activator of breast cancer amplified sequence 3.
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Gururaj AE, Singh RR, Rayala SK, Holm C, den Hollander P, Zhang H, Balasenthil S, Talukder AH, Landberg G, Kumar R
MTA1, a transcriptional activator of breast cancer amplified sequence 3.
Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6670-5. Epub 2006 Apr 14.
- PubMed ID
- 16617102 [ View in PubMed]
- Abstract
Here we define a function of metastasis-associated protein 1 (MTA1), a presumed corepressor of estrogen receptor alpha (ERalpha), 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 ERalpha 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.