Does a novel form of the breast cancer marker protein, MUC1, act as a receptor molecule that modulates signal transduction?

Molecular analysis of a protein highly expressed in human breast cancer, indicates the presence of a polymorphic tandem repeat domain that encodes a conserved 20 amino acid repeat motif rich in serine and threonine residues that in the mature protein, designated MUC1, are linked via O-glycosidic linkages to sugar residues. Recent studies performed in our laboratory have led to the molecular characterization of a novel MUC1 repeat array minus mRNA, generated by an alternative splicing event that deletes the central tandem repeat array and its flanking sequences. The conceptually derived amino acid sequence of the novel MUC1 protein shows that it is identical with the previously reported transmembrane MUC1 amino acid sequence except for the deletion of the central 20 amino acid tandem repeat array and sequences immediately flanking the repeat array. This indicates that the novel MUC1 protein, which is devoid of the "hallmark" feature of mucins, the tandem repeat array, may be functionally different to the much larger, heavily glycosylated polymorphic repeat array containing MUC1 proteins, that affect cell-cell interactions. Based on an analysis of its peptide sequence, we propose the hypothesis that the novel MUC1 protein may act as a receptor molecule that modulates signal transduction. Preliminary experimental data supports this hypothesis. It appears, therefore, that the MUC1 gene is multifunctional with regard to its protein products- the repeat array containing MUC1 proteins may alter cellular adhesion processes whereas the novel MUC1 protein could be acting as a receptor-like molecule participating in signal transmission.