A STAT-responsive Element in the Promoter of the Episialin/MUC1 Gene Is Involved in Its Overexpression in Carcinoma Cells

Abstract

The mucin-like glycoprotein episialin (MUC1) is highly overproduced by a number of human carcinomas. We have shown previously in a variety of mammalian cell lines that overexpression of this very large transmembrane molecule diminishes cellular adhesion, suggesting that episialin/MUC1 overexpression may play an important role in tumor invasion and metastasis. By using in situhybridization, we show here that episialin/MUC1 mRNA expression can be increased more than 10-fold in breast carcinoma cells relative to the expression in adjacent normal breast epithelium. In search of the molecular mechanism of this overexpression, we observed that the episialin/MUC1 promoter contains a candidate binding site for transcription factors of the STAT family ∼500 base pairs upstream of the transcription start site. Cytokines and/or growth factors such as interleukin-6 or interferon-γ can activate STATs. In the human breast carcinoma cell line T47D, both compounds are able to stimulate transcription of a luciferase reporter gene under the control of a 750-base pair MUC1 promoter fragment proximal to the transcription start site. The observed increase is entirely mediated by the single STAT-binding site, since mutation of this site abolishes stimulation of the reporter by interleukin-6 and interferon-γ. In addition, mutation of the STAT site also decreased the promoter activity in nonstimulated T47D cells, suggesting that the STAT-binding site is among the elements that are involved in the overexpression of MUC1 in tumor cells. The mucin-like glycoprotein episialin (MUC1) is highly overproduced by a number of human carcinomas. We have shown previously in a variety of mammalian cell lines that overexpression of this very large transmembrane molecule diminishes cellular adhesion, suggesting that episialin/MUC1 overexpression may play an important role in tumor invasion and metastasis. By using in situhybridization, we show here that episialin/MUC1 mRNA expression can be increased more than 10-fold in breast carcinoma cells relative to the expression in adjacent normal breast epithelium. In search of the molecular mechanism of this overexpression, we observed that the episialin/MUC1 promoter contains a candidate binding site for transcription factors of the STAT family ∼500 base pairs upstream of the transcription start site. Cytokines and/or growth factors such as interleukin-6 or interferon-γ can activate STATs. In the human breast carcinoma cell line T47D, both compounds are able to stimulate transcription of a luciferase reporter gene under the control of a 750-base pair MUC1 promoter fragment proximal to the transcription start site. The observed increase is entirely mediated by the single STAT-binding site, since mutation of this site abolishes stimulation of the reporter by interleukin-6 and interferon-γ. In addition, mutation of the STAT site also decreased the promoter activity in nonstimulated T47D cells, suggesting that the STAT-binding site is among the elements that are involved in the overexpression of MUC1 in tumor cells. mucin-1 electrophoretic mobility shift assay fetal bovine serum intercellular adhesion molecule-1 interferon interleukin-6 signal transducer and activator of transcription Dulbecco's modified Eagle's medium base pair phosphate-buffered saline Episialin/MUC11 (also known as MUC1, PEM, CA 15-3 antigen, or EMA) is a transmembrane molecule with a large extracellular mucin-like domain. In normal cells episialin/MUC1 is exclusively present at the apical side of the cell, but in carcinoma cells normal polarization is lost and episialin/MUC1 co-localizes with adhesion molecules such as integrins and cadherins. The long and relatively rigid extracellular domain of episialin/MUC1 can shield these adhesion molecules and diminish cellular adhesion, if present at a sufficiently high density on the cell surface (1Ligtenberg M.J. Buijs F. Vos H.L. Hilkens J. Cancer Res. 1992; 52: 2318-2324PubMed Google Scholar, 2Wesseling J. van der Valk S.W. Vos H.L. Sonnenberg A. Hilkens J. J. Cell Biol. 1995; 129: 255-265Crossref PubMed Scopus (442) Google Scholar, 3Wesseling J. van der Valk S.W. Hilkens J. Mol. Biol. Cell. 1996; 7: 565-577Crossref PubMed Scopus (358) Google Scholar). Overexpression of episialin/MUC1 in carcinoma cells has been frequently reported (4Hilkens J. Buijs F. Hilgers J. Hageman P. Calafat J. Sonnenberg A. van der Valk M. Int. J. Cancer. 1984; 34: 197-206Crossref PubMed Scopus (402) Google Scholar, A. Hageman Hilkens J. Hilgers J. Google Scholar, M. M. PubMed Scopus Google and is to have a on cellular as of the adhesion has been shown to invasion and of carcinoma cells J. Google Scholar, M. M. Cancer 1996; Scholar, 1996; PubMed Scopus Google Scholar). we have that episialin/MUC1 also an important role in invasion and in J. Vos H.L. J. J. J. M. van der Valk S.W. F. M. in and Scholar). episialin/MUC1 more than and J. and J. episialin/MUC1 show a of tumor J. Biol. 1995; PubMed Scopus Google have shown that episialin overexpression in of with PubMed Google Scholar, Cancer PubMed Scopus Google Scholar, F. A. Hilkens J. J. PubMed Scopus Google Scholar). is also the that is in the CA 15-3 assay to of breast and is a molecule that is as of the molecules to be for breast the of episialin/MUC1 overexpression in tumor cells is of In cell has been shown that episialin/MUC1 overexpression is frequently the of a the episialin/MUC1 gene under the control of an J. PubMed Google Scholar, F. A. P. PubMed Google and is with a role in of these the of episialin/MUC1 overexpression in carcinoma cells have been M. M. PubMed Scopus Google Scholar, Cancer PubMed Scopus Google have shown that the episialin/MUC1 mRNA is increased in breast carcinoma relative to adjacent normal epithelium. these using mRNA of are since both breast carcinoma and normal breast of cell these that overexpression of episialin/MUC1 with increased mRNA mRNA in breast carcinoma cell lines also are increased in to cells M.J. Vos H.L. Hilkens J. J. Biol. PubMed Google Scholar). The of and Cancer PubMed Scopus Google that the episialin/MUC1 mRNA to may be by of but of overexpression are as since the of overexpression is than the of that overexpression of episialin/MUC1 in carcinoma cells is the of of a transcription or of a are in carcinoma cells and to the of these cells. an to such a or we the normal of the episialin/MUC1 gene a we factors that have been shown to episialin is known to episialin/MUC1 expression in cell lines breast PubMed Scopus Google Scholar). F. M. F. M. episialin/MUC1 expression is by cells are on J. J. M.J. J. Cell 1992; Google Scholar). of expression by is in line with the increased expression of human episialin (4Hilkens J. Buijs F. Hilgers J. Hageman P. Calafat J. Sonnenberg A. van der Valk M. Int. J. Cancer. 1984; 34: 197-206Crossref PubMed Scopus (402) Google are breast carcinoma cells may J. 1995; Google Scholar, Cancer Res. 1995; Google that to stimulation of episialin and and of transcription of this family and and to the transcription of a large number of A. PubMed Scopus Google Scholar). In to and may also be by of the such as interleukin-6 is by a variety of cells among are cells a Cytokines in is that of are in J. A. J. Cell. PubMed Scopus Google in the breast carcinoma cell lines T47D and an and decreased adhesion A. PubMed Scopus Google Scholar, A. PubMed Scopus Google that overexpression of the we that STAT be of the important of episialin/MUC1 that be involved in episialin/MUC1 is as STAT-binding is in human and is present upstream of the transcription start site J. Biol. PubMed Google Scholar, H.L. Hilkens J. Res. PubMed Scopus Google Scholar, A. J. J. Biol. PubMed Google and is the proximal that has been to the for episialin/MUC1 expression in cell lines A. J. J. Biol. PubMed Google M. A. PubMed Scopus Google Scholar). der and J. der and J. STAT are known to be in a number of breast carcinoma J. Cancer. 1995; PubMed Scopus Google Scholar, A. Cell Google Scholar). In addition, a Cell. PubMed Scopus Google that can as an show for the that the expression of the episialin/MUC1 gene is highly in breast and that STAT transcription factors to this overexpression of of with in the domain of episialin that this molecule is in breast (4Hilkens J. Buijs F. Hilgers J. Hageman P. Calafat J. Sonnenberg A. van der Valk M. Int. J. Cancer. 1984; 34: 197-206Crossref PubMed Scopus (402) Google Scholar, A. Hageman Hilkens J. Hilgers J. Google Scholar). the domain of episialin on normal breast cells that or binding of the episialin molecules more the of the to A. J. J. J. Int. J. Cancer. PubMed Scopus Google Scholar, J. J. Cell Biol. Google Scholar, F. J. J. 1996; PubMed Scopus Google Scholar, J. J. J. Biol. 1996; PubMed Scopus Google Scholar). the increased of episialin with tumor cells as reported in the be by in in normal and tumor cells and by overexpression of the episialin/MUC1 In this that are if at that overexpression of episialin/MUC1 in breast carcinoma cells The of M. M. PubMed Scopus Google and and Cancer PubMed Scopus Google that increased episialin mRNA are for the overexpression of episialin/MUC1 in breast carcinoma cells. on and are to in show for the that the episialin/MUC1 gene is in breast relative to normal breast for the increased episialin/MUC1 mRNA in carcinoma cells is of the the in the normal breast cell line and in the tumor cell lines M. J. Cell. PubMed Scopus Google and T47D is In episialin/MUC1 mRNA is very is with a role of episialin as a to an mRNA are of the gene more of the promoter by The mechanism is in the of as shown by and Cancer PubMed Scopus Google but is able to of overexpression can the of mRNA overexpression in and cell promoter mutation is to of the by M.J. Vos H.L. Hilkens J. J. Biol. PubMed Google and and Cancer PubMed Scopus Google that the expression of both can be on the of in the number of is to the number of gene as on in the promoter as a mechanism of overexpression and in of gene as the important mechanism of episialin/MUC1 mRNA that the episialin/MUC1 promoter can be by STAT transcription factors a STAT-binding site in The and of this site is in the of H.L. Hilkens J. Res. PubMed Scopus Google and J. Biol. PubMed Google and the is to that of the binding site for and in the promoter M.J. J. Biol. PubMed Google Scholar, P. J. A. F. der J. Biol. PubMed Google Scholar). We the that to the STAT site in the episialin/MUC1 promoter as in the of by and in the of is in line with the of and PubMed Scopus Google Scholar, Cell. 1996; PubMed Scopus Google the of growth or serum the contains a luciferase reporter gene by of the episialin/MUC1 promoter the a activity in reporter in the carcinoma cell line T47D, mutation of the STAT site. that a is present in this cell may to overexpression of have been reported in breast J. Cancer. 1995; PubMed Scopus Google Scholar, A. Cell Google Scholar). show a STAT binding that is by of the cells with or also to the but is in using an with a STAT site. The of this has been but may the overexpression of episialin/MUC1 in carcinoma cells. The is in line with the that the is present in the episialin cells is a the activity of the and these a of the promoter activity by in reporter with T47D and cells, episialin/MUC1 increase to the the cells are with we have for the episialin/MUC1 as for has been reported for the J. Biol. Scopus Google this be to the of the promoter to be is in these cells, or to the of the promoter in a in a of normal the of episialin/MUC1 in the cell lines the T47D and can be in cell lines with an or expression episialin/MUC1 can be by or suggesting that the promoter activity in the cells has an the promoter fragment in the may the expression in T47D and cells. show that the of the promoter fragment in the reporter to the of the diminish the the and the luciferase and J. in for the of the episialin to by in of the carcinoma cells may be the of the to to binding site in the episialin/MUC1 the site is for by the previously in the that this has a or for the than The that a can be observed in the be to the of of the promoter activity in the reporter by can be by the of reporter in the can be that by of the promoter a of the STAT site is in an expression of the MUC1 promoter in cells a of the of show for such an of the promoter be observed with a of of elements have been in the episialin/MUC1 A. J. J. Biol. PubMed Google Scholar, A. J. J. J. Biol. 1996; PubMed Scopus Google an at to and a binding site at to The site can an or in the of the and are to be in a may expression of In line with these we that the of of binding to the STAT-binding site in the to episialin/MUC1 expression in the is in cells M.J. J. Cancer Res. Google and cells and or at very of cell In addition, are known to of of episialin/MUC1 of cells can be In this is important to that is an growth in cells, cells and cell frequently high of episialin/MUC1 Cancer Biol. 1992; Google Scholar, PubMed Scopus Google Scholar, F. J. F. 1996; PubMed Google of episialin expression has important for cellular adhesion in cells and normal cells. of the expression of of episialin/MUC1 and the in cell of as has been reported in breast and in and is of the factors for the overexpression of episialin in these cells. Episialin/MUC11 (also known as MUC1, PEM, CA 15-3 antigen, or EMA) is a transmembrane molecule with a large extracellular mucin-like domain. In normal cells episialin/MUC1 is exclusively present at the apical side of the cell, but in carcinoma cells normal polarization is lost and episialin/MUC1 co-localizes with adhesion molecules such as integrins and cadherins. The long and relatively rigid extracellular domain of episialin/MUC1 can shield these adhesion molecules and diminish cellular adhesion, if present at a sufficiently high density on the cell surface (1Ligtenberg M.J. Buijs F. Vos H.L. Hilkens J. Cancer Res. 1992; 52: 2318-2324PubMed Google Scholar, 2Wesseling J. van der Valk S.W. Vos H.L. Sonnenberg A. Hilkens J. J. Cell Biol. 1995; 129: 255-265Crossref PubMed Scopus (442) Google Scholar, 3Wesseling J. van der Valk S.W. Hilkens J. Mol. Biol. Cell. 1996; 7: 565-577Crossref PubMed Scopus (358) Google Scholar). Overexpression of episialin/MUC1 in carcinoma cells has been frequently reported (4Hilkens J. Buijs F. Hilgers J. Hageman P. Calafat J. Sonnenberg A. van der Valk M. Int. J. Cancer. 1984; 34: 197-206Crossref PubMed Scopus (402) Google Scholar, A. Hageman Hilkens J. Hilgers J. Google Scholar, M. M. PubMed Scopus Google and is to have a on cellular as of the adhesion has been shown to invasion and of carcinoma cells J. Google Scholar, M. M. Cancer 1996; Scholar, 1996; PubMed Scopus Google Scholar). we have that episialin/MUC1 also an important role in invasion and in J. Vos H.L. J. J. J. M. van der Valk S.W. F. M. in and Scholar). episialin/MUC1 more than and J. and J. episialin/MUC1 show a of tumor J. Biol. 1995; PubMed Scopus Google Scholar). have shown that episialin overexpression in of with PubMed Google Scholar, Cancer PubMed Scopus Google Scholar, F. A. Hilkens J. J. PubMed Scopus Google Scholar). is also the that is in the CA 15-3 assay to of breast and is a molecule that is as of the molecules to be for breast the of episialin/MUC1 overexpression in tumor cells is of In cell has been shown that episialin/MUC1 overexpression is frequently the of a the episialin/MUC1 gene under the control of an J. PubMed Google Scholar, F. A. P. PubMed Google and is with a role in of these the of episialin/MUC1 overexpression in carcinoma cells have been M. M. PubMed Scopus Google Scholar, Cancer PubMed Scopus Google have shown that the episialin/MUC1 mRNA is increased in breast carcinoma relative to adjacent normal epithelium. these using mRNA of are since both breast carcinoma and normal breast of cell these that overexpression of episialin/MUC1 with increased mRNA mRNA in breast carcinoma cell lines also are increased in to cells M.J. Vos H.L. Hilkens J. J. Biol. PubMed Google Scholar). The of and Cancer PubMed Scopus Google that the episialin/MUC1 mRNA to may be by of but of overexpression are as since the of overexpression is than the of We that overexpression of episialin/MUC1 in carcinoma cells is the of of a transcription or of a are in carcinoma cells and to the of these cells. an to such a or we the normal of the episialin/MUC1 gene a we factors that have been shown to episialin is known to episialin/MUC1 expression in cell lines breast PubMed Scopus Google Scholar). F. M. F. M. episialin/MUC1 expression is by cells are on J. J. M.J. J. Cell 1992; Google Scholar). of expression by is in line with the increased expression of human episialin (4Hilkens J. Buijs F. Hilgers J. Hageman P. Calafat J. Sonnenberg A. van der Valk M. Int. J. Cancer. 1984; 34: 197-206Crossref PubMed Scopus (402) Google are breast carcinoma cells may J. 1995; Google Scholar, Cancer Res. 1995; Google that to stimulation of episialin and and of transcription of this family and and to the transcription of a large number of A. PubMed Scopus Google Scholar). In to and may also be by of the such as interleukin-6 is by a variety of cells among are cells a Cytokines in is that of are in J. A. J. Cell. PubMed Scopus Google in the breast carcinoma cell lines T47D and an and decreased adhesion A. PubMed Scopus Google Scholar, A. PubMed Scopus Google that overexpression of the we that STAT be of the important of episialin/MUC1 that be involved in episialin/MUC1 is as STAT-binding is in human and is present upstream of the transcription start site J. Biol. PubMed Google Scholar, H.L. Hilkens J. Res. PubMed Scopus Google Scholar, A. J. J. Biol. PubMed Google and is the proximal that has been to the for episialin/MUC1 expression in cell lines A. J. J. Biol. PubMed Google M. A. PubMed Scopus Google Scholar). der and J. der and J. STAT are known to be in a number of breast carcinoma J. Cancer. 1995; PubMed Scopus Google Scholar, A. Cell Google Scholar). In addition, a Cell. PubMed Scopus Google that can as an show for the that the expression of the episialin/MUC1 gene is highly in breast and that STAT transcription factors to this overexpression of of with in the domain of episialin that this molecule is in breast (4Hilkens J. Buijs F. Hilgers J. Hageman P. Calafat J. Sonnenberg A. van der Valk M. Int. J. Cancer. 1984; 34: 197-206Crossref PubMed Scopus (402) Google Scholar, A. Hageman Hilkens J. Hilgers J. Google Scholar). the domain of episialin on normal breast cells that or binding of the episialin molecules more the of the to A. J. J. J. Int. J. Cancer. PubMed Scopus Google Scholar, J. J. Cell Biol. Google Scholar, F. J. J. 1996; PubMed Scopus Google Scholar, J. J. J. Biol. 1996; PubMed Scopus Google Scholar). the increased of episialin with tumor cells as reported in the be by in in normal and tumor cells and by overexpression of the episialin/MUC1 In this that are if at that overexpression of episialin/MUC1 in breast carcinoma cells The of M. M. PubMed Scopus Google and and Cancer PubMed Scopus Google that increased episialin mRNA are for the overexpression of episialin/MUC1 in breast carcinoma cells. on and are to in show for the that the episialin/MUC1 gene is in breast relative to normal breast for the increased episialin/MUC1 mRNA in carcinoma cells is of the the in the normal breast cell line and in the tumor cell lines M. J. Cell. PubMed Scopus Google and T47D is In episialin/MUC1 mRNA is very is with a role of episialin as a to an mRNA are of the gene more of the promoter by The mechanism is in the of as shown by and Cancer PubMed Scopus Google but is able to of overexpression can the of mRNA overexpression in and cell promoter mutation is to of the by M.J. Vos H.L. Hilkens J. J. Biol. PubMed Google and and Cancer PubMed Scopus Google that the expression of both can be on the of in the number of is to the number of gene as on in the promoter as a mechanism of overexpression and in of gene as the important mechanism of episialin/MUC1 mRNA that the episialin/MUC1 promoter can be by STAT transcription factors a STAT-binding site in The and of this site is in the of H.L. Hilkens J. Res. PubMed Scopus Google and J. Biol. PubMed Google and the is to that of the binding site for and in the promoter M.J. J. Biol. PubMed Google Scholar, P. J. A. F. der J. Biol. PubMed Google Scholar). We the that to the STAT site in the episialin/MUC1 promoter as in the of by and in the of is in line with the of and PubMed Scopus Google Scholar, Cell. 1996; PubMed Scopus Google the of growth or serum the contains a luciferase reporter gene by of the episialin/MUC1 promoter the a activity in reporter in the carcinoma cell line T47D, mutation of the STAT site. that a is present in this cell may to overexpression of have been reported in breast J. Cancer. 1995; PubMed Scopus Google Scholar, A. Cell Google Scholar). show a STAT binding that is by of the cells with or also to the but is in using an with a STAT site. The of this has been but may the overexpression of episialin/MUC1 in carcinoma cells. The is in line with the that the is present in the episialin cells is a the activity of the and these a of the promoter activity by in reporter with T47D and cells, episialin/MUC1 increase to the the cells are with we have for the episialin/MUC1 as for has been reported for the J. Biol. Scopus Google this be to the of the promoter to be is in these cells, or to the of the promoter in a in a of normal the of episialin/MUC1 in the cell lines the T47D and can be in cell lines with an or expression episialin/MUC1 can be by or suggesting that the promoter activity in the cells has an the promoter fragment in the may the expression in T47D and cells. show that the of the promoter fragment in the reporter to the of the diminish the the and the luciferase and J. in for the of the episialin to by in of the carcinoma cells may be the of the to to binding site in the episialin/MUC1 the site is for by the previously in the that this has a or for the than The that a can be observed in the be to the of of the promoter activity in the reporter by can be by the of reporter in the can be that by of the promoter a of the STAT site is in an expression of the MUC1 promoter in cells a of the of show for such an of the promoter be observed with a of of elements have been in the episialin/MUC1 A. J. J. Biol. PubMed Google Scholar, A. J. J. J. Biol. 1996; PubMed Scopus Google an at to and a binding site at to The site can an or in the of the and are to be in a may expression of In line with these we that the of of binding to the STAT-binding site in the to episialin/MUC1 expression in the is in cells M.J. J. Cancer Res. Google and cells and or at very of cell In addition, are known to of of episialin/MUC1 of cells can be In this is important to that is an growth in cells, cells and cell frequently high of episialin/MUC1 Cancer Biol. 1992; Google Scholar, PubMed Scopus Google Scholar, F. J. F. 1996; PubMed Google of episialin expression has important for cellular adhesion in cells and normal cells. of the expression of of episialin/MUC1 and the in cell of as has been reported in breast and in and is of the factors for the overexpression of episialin in these cells. of with in the domain of episialin that this molecule is in breast (4Hilkens J. Buijs F. Hilgers J. Hageman P. Calafat J. Sonnenberg A. van der Valk M. Int. J. Cancer. 1984; 34: 197-206Crossref PubMed Scopus (402) Google Scholar, A. Hageman Hilkens J. Hilgers J. Google Scholar). the domain of episialin on normal breast cells that or binding of the episialin molecules more the of the to A. J. J. J. Int. J. Cancer. PubMed Scopus Google Scholar, J. J. Cell Biol. Google Scholar, F. J. J. 1996; PubMed Scopus Google Scholar, J. J. J. Biol. 1996; PubMed Scopus Google Scholar). the increased of episialin with tumor cells as reported in the be by in in normal and tumor cells and by overexpression of the episialin/MUC1 In this that are if at that overexpression of episialin/MUC1 in breast carcinoma cells The of M. M. PubMed Scopus Google and and Cancer PubMed Scopus Google that increased episialin mRNA are for the overexpression of episialin/MUC1 in breast carcinoma cells. on and are to in show for the that the episialin/MUC1 gene is in breast relative to normal breast epithelium. for the increased episialin/MUC1 mRNA in carcinoma cells is of the the in the normal breast cell line and in the tumor cell lines M. J. Cell. PubMed Scopus Google and T47D is In episialin/MUC1 mRNA is very is with a role of episialin as a to an mRNA are of the gene more of the promoter by The mechanism is in the of as shown by and Cancer PubMed Scopus Google but is able to of overexpression can the of mRNA overexpression in and cell promoter mutation is to of the by M.J. Vos H.L. Hilkens J. J. Biol. PubMed Google and and Cancer PubMed Scopus Google that the expression of both can be on the of in the number of is to the number of gene as on in the promoter as a mechanism of overexpression and in of gene as the important mechanism of episialin/MUC1 mRNA that the episialin/MUC1 promoter can be by STAT transcription factors a STAT-binding site in The and of this site is in the of H.L. Hilkens J. Res. PubMed Scopus Google and J. Biol. PubMed Google and the is to that of the binding site for and in the promoter M.J. J. Biol. PubMed Google Scholar, P. J. A. F. der J. Biol. PubMed Google Scholar). We the that to the STAT site in the episialin/MUC1 promoter as in the of by and in the of is in line with the of and PubMed Scopus Google Scholar, Cell. 1996; PubMed Scopus Google Scholar). the of growth or serum the contains a luciferase reporter gene by of the episialin/MUC1 promoter the a activity in reporter in the carcinoma cell line T47D, mutation of the STAT site. that a is present in this cell may to overexpression of have been reported in breast J. Cancer. 1995; PubMed Scopus Google Scholar, A. Cell Google Scholar). show a STAT binding that is by of the cells with or also to the but is in using an with a STAT site. The of this has been but may the overexpression of episialin/MUC1 in carcinoma cells. The is in line with the that the is present in the episialin cells is a the activity of the and these cells. a of the promoter activity by in reporter with T47D and cells, episialin/MUC1 increase to the the cells are with we have for the episialin/MUC1 as for has been reported for the J. Biol. Scopus Google this be to the of the promoter to be is in these cells, or to the of the promoter in a in a of normal the of episialin/MUC1 in the cell lines the T47D and can be in cell lines with an or expression episialin/MUC1 can be by or suggesting that the promoter activity in the cells has an the promoter fragment in the may the expression in T47D and cells. show that the of the promoter fragment in the reporter to the of the diminish the the and the luciferase and J. in for the of the episialin to by in of the carcinoma cells may be the of the to to binding site in the episialin/MUC1 the site is for by the previously in the that this has a or for the than The that a can be observed in the be to the of of the promoter activity in the reporter by can be by the of reporter in the cells. can be that by of the promoter a of the STAT site is in an expression of the MUC1 promoter in cells a of the of show for such an of the promoter be observed with a of of elements have been in the episialin/MUC1 A. J. J. Biol. PubMed Google Scholar, A. J. J. J. Biol. 1996; PubMed Scopus Google an at to and a binding site at to The site can an or in the of the and are to be in a may expression of In line with these we that the of of binding to the STAT-binding site in the to episialin/MUC1 expression in the cells. is in cells M.J. J. Cancer Res. Google and cells and or at very of cell In addition, are known to of of episialin/MUC1 of cells can be In this is important to that is an growth in cells, cells and cell frequently high of episialin/MUC1 Cancer Biol. 1992; Google Scholar, PubMed Scopus Google Scholar, F. J. F. 1996; PubMed Google Scholar). of episialin expression has important for cellular adhesion in cells and normal cells. of the expression of of episialin/MUC1 and the in cell of as has been reported in breast and in and is of the factors for the overexpression of episialin in these cells. We and for and the of the We also van van der and for of the