The Transcription Factor Snail Mediates Epithelial to Mesenchymal Transitions by Repression of Estrogen Receptor Alpha.

@article{citeulike:1921363, abstract = {The estrogen receptor-alpha (ER-alpha, ESR1) is a key regulatory molecule in mammary epithelial cell development. Loss of ER-alpha in breast cancer is correlated with poor prognosis, increased recurrence following treatment, and an elevated incidence of metastasis. A proposed molecular pathway by which ER-alpha acts to constrain invasive growth in breast cancer cells involves direct, ER- alpha dependent expression of MTA3, a cell-type specific component of the Mi-2/NuRD chromatin remodeling complex. MTA3 in turn represses expression of Snail, a transcription factor linked to epithelial to mesenchymal transition (EMT) and cancer metastasis. To elucidate its role(s) in EMT, we expressed Snail in the non-invasive, ER-alpha positive MCF-7 cell line. Snail expression led to decreased cell-cell adhesion and increased cell invasiveness. Further, we observed loss of ER- alpha expression at both the RNA and protein level that was accompanied by direct interaction of Snail with regulatory DNA sequences at the ESR1 locus. A consequence of loss of ER-alpha function in this system was the increased abundance of key components of the transforming growth factor-beta (TGF-beta) signaling pathway. Thus, cross-talk between ER-alpha, Snail and the TGF-beta pathway appears to control critical phenotypic properties of breast cancer cells.}, address = {Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, P.O. Box 12233, 111 TW Alexander Drive, RTP, NC-27709.}, author = {Dhasarathy, Archana and Kajita, Masahiro and Wade, Paul A A. }, citeulike-article-id = {1921363}, doi = {http://dx.doi.org/10.1210/me.2007-0293}, issn = {0888-8809}, journal = {Mol Endocrinol}, month = {August}, posted-at = {2007-11-15 09:47:43}, priority = {2}, title = {The Transcription Factor Snail Mediates Epithelial to Mesenchymal Transitions by Repression of Estrogen Receptor Alpha.}, url = {http://dx.doi.org/10.1210/me.2007-0293}, year = {2007} }

TY - JOUR ID - citeulike:1921363 L3 - citeulike-article-id:1921363 TI - The Transcription Factor Snail Mediates Epithelial to Mesenchymal Transitions by Repression of Estrogen Receptor Alpha. JF - Mol Endocrinol AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, P.O. Box 12233, 111 TW Alexander Drive, RTP, NC-27709. SN - 0888-8809 N2 - The estrogen receptor-alpha (ER-alpha, ESR1) is a key regulatory molecule in mammary epithelial cell development. Loss of ER-alpha in breast cancer is correlated with poor prognosis, increased recurrence following treatment, and an elevated incidence of metastasis. A proposed molecular pathway by which ER-alpha acts to constrain invasive growth in breast cancer cells involves direct, ER- alpha dependent expression of MTA3, a cell-type specific component of the Mi-2/NuRD chromatin remodeling complex. MTA3 in turn represses expression of Snail, a transcription factor linked to epithelial to mesenchymal transition (EMT) and cancer metastasis. To elucidate its role(s) in EMT, we expressed Snail in the non-invasive, ER-alpha positive MCF-7 cell line. Snail expression led to decreased cell-cell adhesion and increased cell invasiveness. Further, we observed loss of ER- alpha expression at both the RNA and protein level that was accompanied by direct interaction of Snail with regulatory DNA sequences at the ESR1 locus. A consequence of loss of ER-alpha function in this system was the increased abundance of key components of the transforming growth factor-beta (TGF-beta) signaling pathway. Thus, cross-talk between ER-alpha, Snail and the TGF-beta pathway appears to control critical phenotypic properties of breast cancer cells. AU - Dhasarathy, Archana AU - Kajita, Masahiro AU - Wade, Paul A PY - 2007/08/30/ UR - http://dx.doi.org/10.1210/me.2007-0293 ER -