Post-transcriptional regulation of a milk membrane protein, the sialomucincomplex (ascites sialoglycoprotein (ASGP)-1/ASGP-2, Rat Muc4), by transforming growth factor beta

Sialomucin complex (SMC, Rat Muc4) is a heterodimeric glycoprotein complex consisting of a mucin subunit ASGP-1 (ascites sialoglycoprotein-1) and a tr ansmembrane subunit ASGP-8, which can act as a ligand for the receptor tyro sine kinase ErbB2. SMC is highly expressed on the surface of ascites 13762 rat mammary adenocarcinoma cells, approximately 100 times the level in lact ating mammary gland and 10(4) times that in virgin mammary gland. SMC is sh arply increased at mid-pregnancy in a manner similar to beta-casein. Unlike beta-casein, SMC appears to be regulated posttranscriptionally. Its transc ript is present in both virgin and pregnant mammary tissue, and SMC synthes is is induced rapidly in cultured primary mammary epithelial cells from eit her normal pregnant or virgin rats. SMC protein, but not transcript, levels are significantly reduced when mammary cells are cultured in Matrigel, a r econstituted basement membrane which stimulates casein expression. SMC prec ursor is synthesized in Matrigel at a 10-fold lower rate. Matrigel has no e ffect on either the level of SMC or its transcript in cultured 13762 mammar y tumor cells. The Matrigel effect on primary mammary and 13762 cells is mi micked by transforming growth factor beta, a component associated with this complex matrix. These results indicate that SMC is a novel product of norm al mammary gland and milk, which is post-transcriptionally regulated by tra nsforming growth factor beta in normal mammary gland, but not in 13762 mamm ary adenocarcinoma cells.