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 protection of epithelia and the metastasis of some tumors. It is a heterodimeric complex, containing a mucin subunit with anti-adhesive activity and a transmembrane subunit with epidermal growth factor-like domains, one of which acts as an intramembrane ligand for ErbB2. Serum, insulin and insulin-like growth factor, but not epidermal growth factor, induce the expression of sialomucin complex in mammary epithelial cells. Induction correlates with sustained, but not transient, activation of extracellular-regulated protein kinase (ERK). MEK inhibitor U0126 blocked the induction, while activated MEK-1 transfected into a rat mammary adenocarcinoma cell line induced a sustained activation of ERK and up-regulated SMC/Muc4 expression. Northern and Western blotting indicated that up-regulation occurred concomitantly at the transcript and protein levels, both of which could be blocked by U0126. These 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.
Zhu
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Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida, FL 33101, USA.
Price-Schiavi
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SA
Carraway
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KL
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006133:Growth Substances / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D048369:MAP Kinase Kinase 1; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055264:Mucin-4; D009077:Mucins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D052116:Sialomucins; D015398:Signal Transduction; D018038:Sodium Selenite / Q000494:pharmacology; D014158:Transcription, Genetic; D014168:Transferrin / Q000494:pharmacology; D015854:Up-Regulation
D002070:Butadienes; D004791:Enzyme Inhibitors; D006133:Growth Substances; D006854:Hydrocortisone; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D055264:Mucin-4; D009077:Mucins; D009570:Nitriles; D017346:Protein Serine-Threonine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D052116:Sialomucins; D018038:Sodium Selenite; D014168:Transferrin; C524660:Muc4 protein, rat; C113580:U 0126