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Analysis of the promoter of the MUC1 gene overexpressed in breast cancer
Author(s) -
Zaretsky Joseph Z.,
Sarid Ronit,
Aylon Yael,
Mittelman Leonid A.,
Wreschner Daniel H.,
Keydar Iafa
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01452-0
Subject(s) - promoter , transcription (linguistics) , gene isoform , muc1 , biology , microbiology and biotechnology , gene , transcription factor , transfection , gene expression , genetics , cancer , linguistics , philosophy
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 Sac I/ Xmn I 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 Sac I/ Xmn I fragment possess transcription activities. Promoter activities associated with the Sac I/ Xmn I 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.