Muc4/sialomucin complex in the mammary gland and breast cancer

MUC4 is a one of the membrane mucins of the mucin gene (MUC) family, charac terized by mucin tandem repeat domains and a transmembrane domain which ass ociates it with the cell plasma membrane. Although MUC4 is encoded by a sin gle gene, it is produced by epithelial cells as a heterodimer through a pro teolytic cleavage mechanism. This heterodimer is found in both membrane and soluble forms associated with epithelia. Functionally, MUC4 is proposed to provide a protective mechanism for vulnerable epithelia, such as those of the airway, eye, female reproductive tract and mammary gland. The protectiv e mechanism(s) may be highjacked by some carcinomas, such as those of the b reast, to increase tumor progression. Two mechanisms are proposed to contri bute to the MUC4 functions. First, MUC4 acts as an anti-adhesive or anti-re cognition barrier at epithelial or tumor cell surfaces. Second, MUC4 can bi nd the receptor tyrosine kinase ErbB2 and alter its cellular signaling. Exp ression of MUC4 in mammary gland is repressed by posttranscriptional mechan isms involving basement membrane and TGF-beta, which are relieved during pr egnancy to permit secretion of MUC4 into milk. These mechanisms are also ab rogated in some breast cancers, providing a scenario for promotion of tumor progression. These observations imply important functions for MUC4 in both normal mammary function and in breast cancer.