Regulation of Sialomucin Complex Expression and Its Effect on HER Receptor Interaction

Abstract : Sialomucin complex (SMC) is a heterodimeric glycoprotein complex consisting of a mucin subunit ASGP-1 (ascites sialoglycoprotein-1) and a transmembrane subunit ASGP-2, which can act as a ligand for the receptor tyrosine kinase ErbB2. SMC is a highly expressed protein on the surface of ascites 13762 rat mammary adenocarcinoma cells, approximately 10(exp 2) times the level in lactating mammary gland and 10(exp 4) times that in virgin mammary gland. SMC is shapely increased at mid-pregnancy in a manner similar to beta-casein. Unlike beta-casein, SMC appears to be regulated posttranscriptionally, as its transcript is present in both virgin and pregnant mammary tissue and SMC synthesis is induced rapidly in cultured primary mammary epithelial cells from either normal pregnant or virgin rats. SMC protein, but not transcript levels, are significantly reduced when mammary cells are cultured in Matrigel, a reconstituted basement membrane which stimulates casein expression. SMC precursor is synthesized in Matrigel at a 10-fold lower rate. Matrigel has no effect on either the level of SMC or its transcript in cultured 13762 mammary tumor cells. These results indicate that SMC is a novel product of normal mammary gland and milk, which is posttranscriptionally regulated in normal mammary gland, but not in 13762 mammary adenocarcinoma cells.