Abstract
Metastasis-associated protein 3 (MTA3) is a cell type-specific subunit of the Mi-2/NuRD transcriptional corepressor complex. In breast cancer cells, MTA3 and the Mi-2/NuRD complex mediate repression of Snail, a transcription factor that promotes epithelial to mesenchymal transitions. Thus, MTA3 functions to maintain a differentiated, epithelial status in breast cancer. Interestingly, in mammary epithelial cells, MTA3 biosynthesis requires both functional estrogen receptor (ER) and estradiol. Here we have investigated the molecular basis for estrogen and ER-dependent expression of MTA3 in breast cancer cells. Molecular dissection of the MTA3 promoter using transient transfection assays identified a composite element required for high-level transcription consisting of an SP1 site in close proximity to a consensus estrogen response element half-site. Depletion of either SP1 or ER-alpha by RNA interference led to loss of MTA3 transcript in multiple breast cancer cell lines, indicating a requirement for both transcription factors in expression of endogenous MTA3. The MTA3 gene thus joins a growing list of loci regulated by both SP1 and ER.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Base Sequence
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism
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Estrogen Receptor alpha / genetics
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Estrogen Receptor alpha / metabolism
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Estrogen Receptor alpha / physiology
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Estrogens / pharmacology
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Estrogens / physiology*
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Female
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Gene Expression Regulation, Neoplastic*
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Genes, Reporter / genetics
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism
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Humans
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Luciferases / analysis
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Luciferases / genetics
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Molecular Sequence Data
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / metabolism
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RNA Interference
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Response Elements / genetics*
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Sp1 Transcription Factor / genetics
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Sp1 Transcription Factor / metabolism
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Sp1 Transcription Factor / physiology*
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Trans-Activators
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Transcription, Genetic
Substances
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Estrogen Receptor alpha
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Estrogens
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MTA3 protein, human
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MTA1 protein, human
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Neoplasm Proteins
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RNA, Messenger
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Repressor Proteins
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Sp1 Transcription Factor
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Trans-Activators
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Luciferases
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MTA2 protein, human
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Histone Deacetylases