Alternative splicing of the human MUC2 gene.

Human colon cancers differ in amounts of MUC2 mucin synthesized. However, it is unclear whether MUC2 encodes a single protein. When clones of human colon cancer cells were assayed with antibodies against the TR2 mucin repeat or non-TR2 epitopes, differences in relative expression of MUC2 proteins suggested multiple immunoreactive forms. RT-PCR analysis detected the established 15kbp MUC2 cDNA and a novel form (designated MUC2.1) lacking the MUC2 TR2 repeat. Sequencing of cDNA and genomic DNA indicated that MUC2.1 results from an alternate splice donor. RT-PCR with splice-junction spanning primers confirmed the expression of MUC2.1 mRNA. Anti-MUC2.1 antibody stained colon cancer cells and normal colon in a pattern different from TR2-specific antibody. The presence of MUC2.1 mucin may help us to explain previous conflicting reports that have attempted to correlate the relative abundance of MUC2 protein and/or mRNA with the biological behavior of colon cancer cells.