First Author | Gururaj AE | Year | 2006 |
Journal | Proc Natl Acad Sci U S A | Volume | 103 |
Issue | 17 | Pages | 6670-5 |
PubMed ID | 16617102 | Mgi Jnum | J:109106 |
Mgi Id | MGI:3625778 | Doi | 10.1073/pnas.0601989103 |
Citation | Gururaj AE, et al. (2006) MTA1, a transcriptional activator of breast cancer amplified sequence 3. Proc Natl Acad Sci U S A 103(17):6670-5 |
abstractText | 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. |