Extracellular regulated kinase (ERK)-dependent regulation of sialomucin complex/rat Muc4 in mammary epithelial cells

Sialomucin complex (SMC, rat Muc4) is a membrane mucin implicated in the pr otection of epithelia and the metastasis of some tumors. It is a heterodime ric complex, containing a mucin subunit with anti-adhesive activity and a t ransmembrane subunit with epidermal growth factor-like domains, one of whic h acts as an intramembrane ligand for ErbB2, Serum, insulin and insulin-lik e growth factor, but not epidermal growth factor, induce the expression of sialomucin complex in mammary epithelial cells, Induction correlates,vith s ustained, but not transient, activation of extracellular-regulated protein kinase (ERK), MEK inhibitor U0126 blocked the induction, while activated ME K-1 transfected into a rat mammary adenocarcinoma cell line induced a susta ined activation of ERK and up-regulated SMC/Muc4 expression, Northern and W estern blotting indicated that up-regulation occurred concomitantly at the transcript and protein levels, both of which could be blocked by U0126. The se results suggest that expression of SMC/Muc4 in mammary epithelial cells is regulated by selected growth factors through an ERK-dependent pathway at the transcript level.