Post-transcriptional regulation of a milk membrane protein, the sialomucin complex (Ascites sialoglycoprotein (ASGP)-1/ASGP-2, rat muc4), by transforming growth factor beta

• Published in: The Journal of biological chemistry 1998-12, Vol.273 (52), p.35228-35237
• Main Authors: Price-Schiavi, S A, Carraway, C A, Fregien, N, Carraway, K L
• Format: Article
• Language: English
• Subjects: Animals; Collagen - pharmacology; Dose-Response Relationship, Drug; Drug Combinations; Female; Gene Expression Regulation; Lactation - drug effects; Lactation - metabolism; Laminin - pharmacology; Mammary Glands, Animal - drug effects; Mammary Glands, Animal - metabolism; Mammary Neoplasms, Animal - metabolism; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Milk Proteins - biosynthesis; Milk Proteins - genetics; Models, Biological; Mucin-4; Mucins - biosynthesis; Mucins - genetics; Pregnancy; Proteoglycans - pharmacology; Rats; RNA Processing, Post-Transcriptional; RNA, Messenger - analysis; Sialoglycoproteins - biosynthesis; Sialoglycoproteins - genetics; Sialomucins; Transforming Growth Factor beta - pharmacology; Tumor Cells, Cultured
• ISSN: 0021-9258
• DOI: 10.1074/jbc.273.52.35228

Sialomucin complex (SMC, Rat Muc4) 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 highly expressed on the surface of ascites 13762 rat mammary adenocarcinoma cells, approximately 100 times the level in lactating mammary gland and 10(4) times that in virgin mammary gland. SMC is sharply increased at mid-pregnancy in a manner similar to beta-casein. Unlike beta-casein, SMC appears to be regulated post-transcriptionally. 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. The Matrigel effect on primary mammary and 13762 cells is mimicked by transforming growth factor beta, a component associated with this complex matrix. These results indicate that SMC is a novel product of normal mammary gland and milk, which is post-transcriptionally regulated by transforming growth factor beta in normal mammary gland, but not in 13762 mammary adenocarcinoma cells.