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MTA1, a transcriptional activator of breast cancer amplified sequence 3

Gururaj, AE ; Singh, RR ; Rayala, SK ; Wigerup, Caroline LU ; den Hollander, P ; Zhang, H ; Balasenthil, S ; Talukder, AH ; Landberg, Göran LU and Kumar, R (2006) In Proceedings of the National Academy of Sciences 103(17). p.6670-6675
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
estrogen receptor, BCAS3, coactivator
in
Proceedings of the National Academy of Sciences
volume
103
issue
17
pages
6670 - 6675
publisher
National Acad Sciences
external identifiers
  • pmid:16617102
  • wos:000237151000046
  • scopus:33646238716
  • pmid:16617102
ISSN
1091-6490
DOI
10.1073/pnas.0601989103
language
English
LU publication?
yes
id
4d2badf6-1890-408d-8b5f-abad52f4c4b3 (old id 410255)
date added to LUP
2016-04-01 11:35:48
date last changed
2021-07-27 01:41:20
@article{4d2badf6-1890-408d-8b5f-abad52f4c4b3,
  abstract     = {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       = {Gururaj, AE and Singh, RR and Rayala, SK and Wigerup, Caroline and den Hollander, P and Zhang, H and Balasenthil, S and Talukder, AH and Landberg, Göran and Kumar, R},
  issn         = {1091-6490},
  language     = {eng},
  number       = {17},
  pages        = {6670--6675},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {MTA1, a transcriptional activator of breast cancer amplified sequence 3},
  url          = {http://dx.doi.org/10.1073/pnas.0601989103},
  doi          = {10.1073/pnas.0601989103},
  volume       = {103},
  year         = {2006},
}