are likely artefactual. Many polymorphisms are observed in the tandem repeat region of the alpha subunit, which has a variable number of repeats. Function Normal In normal functioning, MUC-4 is known to play anti-adhesive roles in the body, such as in lubricating the reproductive lining. It is also found in the respiratory tract - particularly in the trachea and lung - and the digestive tract - in the esophagus and colon - as well as in the visual and auditory systems. In these roles, MUC-4 serves to protect and lubricate the epithelium, which facilitates transport and traps foreign particles. One example of its function in the reproductive lining relates to blastocyst implantation resulting from MUC4 downregulation. It is found to be overexpressed during the luteal phase of menstruation. MUC-4 may also have a role in fetal morphogenic development. MUC-4 is not found in the gallbladder, pancreas, or liver except in abnormal conditions such as cancer. MUC-4, however, may normally be found in bodily fluids like saliva, tears, and milk. In the soluble form, MUC-4 appears to lubricate the epithelial mucosa. Disease MUC-4 is thought to play a role in cancer progression by repressing apoptosis and consequently increasing tumor cell proliferation. The molecular mechanism is thought to be through a MUC-4 complex with ERBB2 receptors, which alters downstream signaling and down regulates CDKN1B. The beta subunit of MUC-4 appears to serve as a ligand that causes the phosphorylation of ErbB2, but does not activate the MAPK or AKT pathways. MUC-4 may also affect HER2 signaling, and result in its stabilization. As a mucin, MUC-4 also alters adhesive properties of the cell. When overexpressed, the disorganization of mucins may reduce adhesion to other cells as well as the extracellular matrix, promoting cancer cell migration and metastasis. Role in cancer Pancreatic MUC4 is often overexpressed in pancreatic adenocarcinomas and has been shown to promote tumor growth and metastasis, though the mechanism by which it does so is not known. MUC4 detection is emerging as a method to diagnose pancreatic cancer, especially since MUC4 is not detectably expressed in normal pancreas and increased expression of MUC-4 suggests a greater progression of the disease. Scientists have recently experimented with MUC4 inhibition in pancreatic cancer using drug delivery methods such as microRNAs. Such efforts have been successful at reducing EGF receptor expression, its downstream signaling, and consequently malignant behavior of the cancer cell such as migration,