Hormonal regulation of metastasis-associated protein 3 transcription in breast cancer cells.

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.

[1]  Anupama E. Gururaj,et al.  Upstream Determinants of Estrogen Receptor-α Regulation of Metastatic Tumor Antigen 3 Pathway* , 2004, Journal of Biological Chemistry.

[2]  P. Wade,et al.  Use of bifunctional cross-linking reagents in mapping genomic distribution of chromatin remodeling complexes. , 2004, Methods.

[3]  Naoyuki Fujita,et al.  Mi-2/NuRD: multiple complexes for many purposes. , 2004, Biochimica et biophysica acta.

[4]  J. Kemper,et al.  Differential regulation of the human progesterone receptor gene through an estrogen response element half site and Sp1 sites , 2004, The Journal of Steroid Biochemistry and Molecular Biology.

[5]  Carlos S. Moreno,et al.  MTA3, a Mi-2/NuRD Complex Subunit, Regulates an Invasive Growth Pathway in Breast Cancer , 2003, Cell.

[6]  Rakesh Kumar.  Another Tie that Binds the MTA Family to Breast Cancer , 2003, Cell.

[7]  E. Fearon.  Connecting estrogen receptor function, transcriptional repression, and E-cadherin expression in breast cancer. , 2003, Cancer cell.

[8]  S. Safe,et al.  Estrogen regulation of transferrin gene expression in MCF-7 human breast cancer cells. , 2002, Journal of molecular endocrinology.

[9]  M. Abdelrahim,et al.  Small Inhibitory RNA Duplexes for Sp1 mRNA Block Basal and Estrogen-induced Gene Expression and Cell Cycle Progression in MCF-7 Breast Cancer Cells* , 2002, The Journal of Biological Chemistry.

[10]  Y. Ip,et al.  Cell movements during gastrulation: snail dependent and independent pathways. , 2002, Current opinion in genetics & development.

[11]  Donald P. McDonnell,et al.  Connections and Regulation of the Human Estrogen Receptor , 2002, Science.

[12]  M. Nieto,et al.  The snail superfamily of zinc-finger transcription factors , 2002, Nature Reviews Molecular Cell Biology.

[13]  E. Carver,et al.  The Mouse Snail Gene Encodes a Key Regulator of the Epithelial-Mesenchymal Transition , 2001, Molecular and Cellular Biology.

[14]  L. Xia,et al.  Sp1 and ETS family transcription factors regulate the mouse Mta2 gene expression. , 2001, Gene.

[15]  J. Qin,et al.  Stable Histone Deacetylase Complexes Distinguished by the Presence of SANT Domain Proteins CoREST/kiaa0071 and Mta-L1* , 2001, The Journal of Biological Chemistry.

[16]  J. Thomsen,et al.  Mechanisms of estrogen action. , 2001, Physiological reviews.

[17]  M. Nakao,et al.  Tsutomu by Methyl-CpG Binding Protein MBD 1 Mechanism of Transcriptional Regulation , 2000 .

[18]  A. Nardulli,et al.  Sp1 binding sites and an estrogen response element half-site are involved in regulation of the human progesterone receptor A promoter. , 2000, Molecular endocrinology.

[19]  E. Ballestar,et al.  Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation , 1999, Nature Genetics.

[20]  A. Bird,et al.  Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. , 1999, Genes & development.

[21]  Weidong Wang,et al.  NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. , 1998, Molecular cell.

[22]  S. Schreiber,et al.  Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex , 1998, Nature.

[23]  D. Reinberg,et al.  The Dermatomyositis-Specific Autoantigen Mi2 Is a Component of a Complex Containing Histone Deacetylase and Nucleosome Remodeling Activities , 1998, Cell.

[24]  A. Wolffe,et al.  A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates with an associated Snf2 superfamily ATPase , 1998, Current Biology.

[25]  K. Struhl.  Histone acetylation and transcriptional regulatory mechanisms. , 1998, Genes & development.

[26]  M. Beato,et al.  Hormone-induced Recruitment of Sp1 Mediates Estrogen Activation of the Rabbit Uteroglobin Gene in Endometrial Epithelium* , 1998, The Journal of Biological Chemistry.

[27]  A. Wolffe,et al.  Structural and functional features of a specific nucleosome containing a recognition element for the thyroid hormone receptor , 1997, The EMBO journal.

[28]  S. Safe,et al.  Functional synergy between the transcription factor Sp1 and the estrogen receptor. , 1997, Molecular endocrinology.

[29]  M. Grunstein.  Histone acetylation in chromatin structure and transcription , 1997, Nature.

[30]  T. Richmond,et al.  Crystal structure of the nucleosome core particle at 2.8 Å resolution , 1997, Nature.

[31]  S. Safe,et al.  Role of estrogen receptor/Sp1 complexes in estrogen-induced heat shock protein 27 gene expression. , 1996, Molecular endocrinology.

[32]  M. Sheikh,et al.  Estradiol regulation of the human retinoic acid receptor alpha gene in human breast carcinoma cells is mediated via an imperfect half-palindromic estrogen response element and Sp1 motifs. , 1995, Cancer research.

[33]  O. Wrange,et al.  Accessibility of a glucocorticoid response element in a nucleosome depends on its rotational positioning , 1995, Molecular and cellular biology.

[34]  G. Nicolson,et al.  A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses. , 1994, The Journal of biological chemistry.

[35]  S. Safe,et al.  Estrogen receptor-Sp1 complexes mediate estrogen-induced cathepsin D gene expression in MCF-7 human breast cancer cells. , 1994, The Journal of biological chemistry.

[36]  O. Wrange,et al.  Translational positioning of a nucleosomal glucocorticoid response element modulates glucocorticoid receptor affinity. , 1993, Genes & development.

[37]  R. Sutherland,et al.  Tamoxifen stimulation of human breast cancer cell proliferation in vitro: a possible model for tamoxifen tumour flare. , 1984, European journal of cancer & clinical oncology.

[38]  Anupama E. Gururaj,et al.  Upstream determinants of estrogen receptor-alpha regulation of metastatic tumor antigen 3 pathway. , 2004, The Journal of biological chemistry.

[39]  Hisashi Koga,et al.  HUGE: a database for human KIAA proteins, a 2004 update integrating HUGEppi and ROUGE , 2004, Nucleic Acids Res..

[40]  G. Nicolson,et al.  Candidate metastasis-associated genes of the rat 13762NF mammary adenocarcinoma , 2004, Breast Cancer Research and Treatment.

[41]  S. Safe.  Transcriptional activation of genes by 17 beta-estradiol through estrogen receptor-Sp1 interactions. , 2001, Vitamins and hormones.

[42]  Osamu Ohara,et al.  HUGE: a database for human large proteins identified by Kazusa cDNA sequencing project , 1999, Nucleic Acids Res..

[43]  K. Kinzler,et al.  A simplified system for generating recombinant adenoviruses. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[44]  Parker Mg.  Transcriptional activation by oestrogen receptors. , 1998 .