Sialomucin complex (rat Muc4) is regulated by transforming growth factor beta in mammary gland by a novel post-translational mechanism

Sialomucin complex (SMC, rat Muc4) is a heterodimeric glycoprotein complex consisting of a mucin subunit ASGP-1 (for ascites sialoglycoprotein-1) and a transmembrane subunit ASGP-2, produced from a single gene and precursor. SMC expression is tightly regulated in mammary gland; the level in lactatin g mammary gland is about 100-fold that in virgin gland. In rat mammary epit helial cells, SMC is post-transcriptionally regulated by Matrigel by inhibi tion of SMC precursor synthesis. SMC is also posttranscriptionally regulate d by transforming growth factor-beta (TGF beta), The repression of SMC expr ession by TGF beta is rapid, is independent of TGF beta-induced cell cycle arrest, and does not require new protein synthesis. Unlike Matrigel, TGF be ta does not reduce SMC protein synthesis, as SMC precursor accumulation is equivalent in TGF beta-treated and untreated cells. Instead, SMC precursor in TGF beta-treated cells is more persistent and does not become processed as rapidly into mature ASGP-1 and ASGP-2, indicating that TGF beta disrupts processing of SMC precursor. These results indicate that SMC, a product of normal mammary gland and milk, is regulated by TGF beta by a novel post-tr anslational mechanism. Thus, SMC is regulated by multiple posttranscription al mechanisms, which serve to repress potential deleterious effects of over expression.