Published in Cancer Detection and Prevention 1995; 19(1).

Molecular cloning of a novel MUC1 protein expressed in breast cancer tissue

DH Wreschner, S Zrihan-Licht, A Baruch & I Keydar

Department of Cell Research and Immunology, Tel Aviv University, Ramat Aviv, 69978 Israel.

The human breast cancer marker protein, MUC1, is a polymorphic transmembrane molecule containing a large extracellular domain that is primarily composed of a variable number of highly conserved 20 amino acid tandem repeats. We report here the nucleotide sequence of a novel MUC1 mRNA. This demonstrates that it is identical to the MUC1 cDNA sequences downstream and upstream to the tandem repeat array of the transmembrane form of MUC1. However, it contains neither the central tandem repeat array itself nor its directly flanking sequences that are deleted by a differential splicing event utilizing splice acceptor and donor sequences 5' and 3' to the tandem repeat array. The splice event retains, downstream to the splice acceptor site, an open reading frame identical to that of the repeat array containing MUC1 thereby generating the novel MUCl/Y protein. The MUCl/Y protein is glycosylated and is readily detected in primary breastcancer tissue samples whereas expression in tissue adjacent to the tumor is undetectable. Molecular characterization presented here, of the novel MUCl/Y molecule lacking the repeat array, suggests that it may act as a new marker protein for human breast cancer and that it is likely to play a role distinct to that of the repeat array positive MUC1 protein.

Paper presented at the International Symposium on the Impact of Biotechnology on Predictive Oncology and Therapy; Boston, Massachusetts; December 11 - 13, 1994; in the section on Risk Factors & Diagnostic Markers.