MTA1, a transcriptional activator of breast cancer amplified sequence 3

Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6670-5. doi: 10.1073/pnas.0601989103. Epub 2006 Apr 14.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • Enhancer Elements, Genetic
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / genetics*
  • Histone Deacetylases / metabolism*
  • Humans
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism*
  • Trans-Activators / chemistry
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism*

Substances

  • BCAS3 protein, human
  • DNA, Neoplasm
  • Estrogen Receptor alpha
  • MTA1 protein, human
  • Neoplasm Proteins
  • Repressor Proteins
  • Trans-Activators
  • Estradiol
  • Histone Deacetylases