A STAT-responsive Element in the Promoter of the Episialin/MUC1 Gene Is Involved in Its Overexpression in Carcinoma Cells
| Autor: | I Gaemers, John Hilkens, S W van der Valk, H H Volders, H. L. Vos |
|---|---|
| Přispěvatelé: | Other departments |
| Rok vydání: | 2001 |
| Předmět: |
STAT3 Transcription Factor
Transcription Genetic Breast Neoplasms Biology Response Elements Biochemistry Interferon-gamma Transcription (biology) Tumor Cells Cultured Humans RNA Messenger Binding site Promoter Regions Genetic skin and connective tissue diseases Cell adhesion neoplasms Molecular Biology Transcription factor Gene MUC1 Regulation of gene expression Binding Sites Interleukin-6 Mucin-1 Cell Biology Molecular biology DNA-Binding Proteins Gene Expression Regulation Neoplastic STAT1 Transcription Factor Trans-Activators Female |
| Zdroj: | Journal of biological chemistry, 276(9), 6191-6199. American Society for Biochemistry and Molecular Biology Inc. |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m009449200 |
| Popis: | 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 situ hybridization, 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 approximately 500 base pairs upstream of the transcription start site. Cytokines and/or growth factors such as interleukin-6 or interferon-gamma 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-gamma. 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. |
| Databáze: | OpenAIRE |
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