Expression of Mucin-like 1 (MUCL1) in the Major Salivary Glands

Mucin-like 1 (MUCL1)/Small Breast Epithelial Mucin (SBEM) has a restricted expression pattern, being expressed only in breast cancers and salivary glands. Multiple studies have identified MUCL-1 as a putative breast cancer marker gene. MUCL-1 encodes a glycosylated, secreted protein with 3 octapeptide core motifs similar to those found in mucins. A host defence function for MUCL1 has been hypothesised but to date MUCL1 has only been studied in breast cancers. Objectives: To characterise the genomic organisation and expression pattern of MUCL1. Methods: RNA from major salivary glands, primary breast tumours and a range of cell lines was used for RT-PCR. Protein expression in major and minor salivary glands and airway submucosal glands was determined. Results: Human MUCL1 contains 4 exons, spans 4kB and is localised to chromosome 12q13. MUCL1 orthologues are not found in rodents, but MUCL1 appears to be distantly related to a number of rodent salivary gland proteins including Spt-1 and Spt-2. mRNA expression was seen in salivary gland and breast cancer tissue and oro-pharyngeal, lung and breast cancer cell lines. We identified a splice variant of the human gene with novel 5' sequence. This transcript was cloned from salivary gland RNA and indicated constitutive expression of both mRNAs. The novel transcript, generated from an alternative 5' exon, 16kB upstream of exon 2, encodes a 85 amino acid protein lacking a signal peptide and thus protein secretion is not predicted. MUCL1 was present in intercalated ducts of major salivary glands in a pattern distinct from other salivary gland proteins. It is not expressed in minor mucosal glands or airway submucosal glands. Conclusion: Our data suggests that MUCL1 is expressed in a population of duct cells from major salivary glands and generates protein isoforms through the use of distinct promoters.