Analysis of the promoter of the MUC1 gene overexpressed in breast cancer

Joseph Z. Zaretsky*, Ronit Sarid, Yael Aylon, Leonid A. Mittelman, Daniel H. Wreschner, Iafa Keydar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The MUC1 gene encodes a mucin glycoprotein and is overexpressed in breast cancer. Knowledge of the mechanisms leading to MUC1 overexpression may help in the development of molecular approaches for breast cancer therapy. In order to study the regulation of the MUC1 gene transcription, we analyzed functional activities of various deletion mutants of the MUC1 promoter. We established that transcriptional cis-elements present in the SacI/XmnI fragment of the promoter are competent and sufficient for expression of, at least, tandem repeats containing isoform(s) of the MUC1 protein. CAT transfection analysis showed that both the 3' and 5' regions of the SacI/XmnI fragment possess transcription activities. Promoter activities associated with the SacI/XmnI fragment were confirmed by a RNase protection assay, which demonstrated multiple transcription start sites (TSSs) in the MUC1 gene transcribed in epithelial T47D cells. We show that treatment of the T47D cells with TGFβ1 leads to activation of additional TSSs in the MUC1 gene. The roles of the structural and functional properties of the MUC1 promoter in MUC1 gene transcription are discussed. Copyright (C) 1999 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)189-195
Number of pages7
JournalFEBS Letters
Volume461
Issue number3
DOIs
StatePublished - 19 Nov 1999

Funding

FundersFunder number
Barbara Friedman Fund
Susan G. Komen
Israel Cancer Association
Tel Aviv University

    Keywords

    • CAT assay
    • MUC1 gene
    • Promoter
    • Transcription start site

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