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

FEBS Letters

Mittelman, Leonid A.¹  Zaretsky, Joseph Z.³  Keydar, Iafa³  Sarid, Ronit²  Aylon, Yael³  Wreschner, Daniel H.³ 

[1] Interdepartmental Core Facility, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel;Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel;Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel

关键词: MUC1 gene;    Promoter;    CAT assay;    Transcription start site;   

DOI  :  10.1016/S0014-5793(99)01452-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown