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

The MUC1 gene encodes a mucin glycoprotein and is overexpressed in breast c ancer. Knowledge of the mechanisms leading to MUC1 overexpression may help in the development of molecular approaches for breast cancer therapy, In or der to study the regulation of the MUC1 gene transcription, we analyzed fun ctional activities of various deletion mutants of the MUC1 promoter, We est ablished that transcriptional cis-elements present in the SacI/XmnI fragmen t 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 S acI/XmnI fragment were confirmed by a RNase protection assay, which demonst rated multiple transcription start sites (TSSs) in the MUC1 gene transcribe d in epithelial T47D cells. We show that treatment of the T47D cells with T GF beta 1 leads to activation of additional TSSs in the MUC1 gene. The role s of the structural and functional properties of the MUC1 promoter in MUC1 gene transcription are discussed. (C) 1999 Federation of European Biochemic al Societies.