Ascites 13762 rat mammary
adenocarcinoma cells express abundantly on their cell surfaces a heterodimeric
glycoprotein complex composed of a
sialomucin ascites sialoglycoprotein (ASGP)-1 and a transmembrane subunit
ASGP-2. The latter, which contains two
epidermal growth factor-like domains, binds the
receptor tyrosine kinase p185(neu), suggesting that the complex is bifunctional as well as heterodimeric. Immunoblot analyses using
monoclonal antibodies prepared against the complex demonstrate high levels of expression in rat lactating mammary gland and colon. Immunolocalization studies with anti-ASGP-2 indicate that
ASGP-2 is present in these two tissues in the apical regions of secretory epithelial cells. Both mammary gland and colon contain a soluble, secretable form of
ASGP-2, which is not found in the
ascites cells; milk and mammary gland also have the membrane form. Immunoblot analyses using a COOH-terminal-specific polyclonal antibody indicate that the soluble form of
ASGP-2 is missing its COOH-terminal domains. Both the soluble and membrane forms of
ASGP-2 are similar to the membrane-associated form from the 13762
adenocarcinoma with respect to Mr, antigenicity, and association with
ASGP-1. The presence of
ASGP-1 in milk suggests that it is a candidate for the uncharacterized high Mr milk
mucin, MUCX.
ASGP-2 expression is up-regulated in mammary gland during pregnancy, because it is undetectable in virgin and early pregnant rats but abundant in the gland from late pregnant and lactating animals. However, compared with the lactating mammary gland, the 13762
ascites cells overexpress
ASGP-2 by more than 100-fold, which may contribute to their
malignancy. These combined results indicate that
sialomucin complex is a unique secreted product in the mammary gland and colon, whose behavior is different from that in the mammary
ascites tumors, and which may play important roles in mammary and intestinal physiology.