CHARACTERIZATION AND MOLECULAR-CLONING OF A NOVEL MUC1 PROTEIN, DEVOID OF TANDEM REPEATS, EXPRESSED IN HUMAN BREAST-CANCER TISSUE

The human breast cancer marker protein, MUC1, is a polymorphic transme mbrane molecule containing a large extracellular domain that is primar ily composed of a variable number of highly conserved 20-amino-acid ta ndem repeats. We report here the detection of a novel invariantly size d 1.2-kb MUC1 mRNA, in addition to the large polymorphic mRNAs, by pro bing Northern blots with MUC1-cDNA-unique-slquence probes. The nucleot ide sequence of this novel MUC1 mRNA demonstrates that it is identical to the MUC1 cDNA sequences downstream and upstream to the tandem-repe at array of the transmembrane form of MUC1. However, it contains neith er the central tandem repeat array itself nor its directly flanking se quences that are deleted by a differential splicing event utilizing sp lice 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 M UC1 thereby generating the novel MUC1/Y protein. Cells transiently tra nsfected with the novel MUC1/Y cDNA express the MUC1/Y protein that is modified by glycosylation. The MUC1/Y protein is also readily detecte d in human breast cancer cells grown in vitro. Furthermore, primary br east cancer tissue samples demonstrate significant levels of the MUC1/ Y protein whereas expression in tissue adjacent to the tumor is undete ctable. Molecular characterization presented here, of the novel MUC1/Y molecule lacking the repeat array, suggests that it is likely to play a role distinct to that of the polymorphic repeat-array-positive MUC1 protein and that it may act as a new marker protein for human breast cancer.