MTA1, a transcriptional activator of breast cancer amplified sequence 3

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.

Singh, RR (author)
Rayala, SK (author)
Wigerup, CarolineLund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups(Swepub:lu)pat-cho (author)
den Hollander, P (author)
Zhang, H (author)
Balasenthil, S (author)
Talukder, AH (author)
Landberg, GöranLund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups(Swepub:lu)pat-gla (author)
Kumar, R (author)
Patologi, MalmöForskargrupper vid Lunds universitet (creator_code:org_t)

In:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences103:17, s. 6670-66751091-64900027-8424

By the author/editor: Gururaj, AE; Singh, RR; Rayala, SK; Wigerup, Carolin ...; den Hollander, P; Zhang, H; show more...; Balasenthil, S; Talukder, AH; Landberg, Göran; Kumar, R; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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