Breast Mucin and Associated Antigens in Diagnosis and Therapy

Abstract

The human milk fat globule (HMFG) membrane has been the source of antigens for the production of polyclonal and monoclonal antibodies against normal and malignant breast epithelial cells that have found important applications in diagnosis and therapy of breast cancer (Ceriani et al., 1977). Monoclonal antibodies (MoAbs) prepared against the HMFG membrane, for the first time, identified a highly glycosylated, large molecular weight glycoprotein (breast mucin) as a major component of the surface membrane of breast epithelial cells (Ceriani et al, 1983). In addition, MoAbs against smaller glycoproteins of the HMFG have identified new and potentially important components of breast epithelial cell membranes, namely two glycoproteins of 70 kDa and a 46 kDa, respectively (Ceriani et al., 1983; Peterson et al, 1990). The 70 kDa glycoprotein (BA70) has been shown to be associated with the breast mucin by disulfide linkages, suggesting it to be a putative linker protein (Duwe et al., 1989) for the breast mucin. The 46 kDa glycoprotein (BA46) appears to be a member of a family of proteins having a domain with homology with the C1C2 domain of human coagulation factors V and VIII (Larocca et al, 1991). In this paper we will summarize the characteristics of the breast mucin and the 46 kDa antigen, present evidence on their epitopic heterogeneity, and suggest possible molecular strategy for selecting the most appropriate MoAbs for use in breast cancer diagnosis and therapy.