Mta1, a Transcriptional Activator of Breast Cancer Amplified Sequence 3.
From: Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Apr 2006
- ISSN: 0027-8424
- Volume: 103
- Issue: 17
- Pages: 6670-5
- Medium: Print
- Language: English
- Citation (JAMA): Gururaj Anupama E, Singh Rajesh R, Rayala Suresh K, et al. Mta1, a Transcriptional Activator of Breast Cancer Amplified Sequence 3.. Proc. Natl. Acad. Sci. U.S.A. Apr 2006;103:6670-5
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.
Mesh Headings (Keywords): Acetylation, Amino Acid Sequence, Base Sequence, Binding Sites, Breast Neoplasms, Cell Line, Tumor, DNA, Neoplasm, Enhancer Elements (Genetics), Estradiol, Estrogen Receptor alpha, Female, Gene Expression Regulation, Neoplastic, Histone Deacetylases, Humans, Molecular Sequence Data, Neoplasm Proteins, Repressor Proteins, Trans-Activators
Check for Full Text / PubMed Unique Identifier (PMID): 16617102
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