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

Citations Over TimeTop 10% of 2001 papers

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 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.

Related Papers

• → Human DF3/MUC1 carcinoma-associated protein functions as an oncogene(2003)193 cited
• → Growth Hormone Activation of Stat 1, Stat 3, and Stat 5 in Rat Liver(1996)228 cited
• → Prognostic significance of muc1 epithelial mucin expression in breast cancer*1(1995)199 cited
• → Expression of Different Glycoforms of Membrane Mucin(MUC1) and Secretory Mucin (MUC2, MUC5AC and MUC6) in Pancreatic Neoplasms(2003)44 cited
• → Expression of STAT 1, STAT 2 and STAT 4 in primary hepatocellular carcinoma and its significance(2004)