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

Oncogene volume 19, pages 4354–4361 (2000)Cite this article

Abstract

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.

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Acknowledgements

We thank Dr Michael Weber, University of Virginia, for generously providing the plasmid pCMV-HA/Mek-1 (S218/222D) use for transfection studies. This research was supported in part by Grant CA52498 from the National Institutes of Health, a predoctoral fellowship DAMD17-97-1-7151 from the Department of the Army Breast Cancer Research Program and by the Sylvester Comprehensive Cancer Center of the University of Miami.

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  1. Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, 33101, Florida, FL, USA

    Xiaoyun Zhu, Shari A Price-Schiavi & Kermit L Carraway

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Zhu, X., Price-Schiavi, S. & Carraway, K. Extracellular regulated kinase (ERK)-dependent regulation of sialomucin complex/rat Muc4 in mammary epithelial cells. Oncogene 19, 4354–4361 (2000). https://doi.org/10.1038/sj.onc.1203781

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