Embryo implantation involves regulated interactions between components of the external surface of the blastocyst and the apical aspect of the uterine epithelium. A thick glycocalyx is found at the apical surface of the uterine epithelium under most conditions. Biochemical studies demonstrate that mucin glycoproteins are the major components of this surface coat. MUC1 has been identified as a key mucin component of the uterine epithelium in all species examined to date. In normal epithelia, MUC1 provides protection from microbial and enzymatic attack. In this regard, MUC1 null mice are predisposed to reproductive tract inflammation. Furthermore, it has been shown that MUC1 is removed either throughout the luminal uterine epithelia or locally, at implantation sites during the receptive uterine state. In vitro studies demonstrate that high level MUC1 expression is sufficient to prevent embryo attachment to human cell lines or polarized mouse uterine epithelial cells. Thus, MUC1 is proposed to perform a general barrier function at the surface of reproductive tract epithelia requiring removal to support embryo attachment. Different species have developed unique strategies to achieve this goal. In some cases, this primarily involves a reduction in MUC1 expression throughout the uterus while in other cases a local stimulation of MUC1 release is likely. In addition, MUC1 serves both as a marker of tumor progression and therapeutic target. MUC1 fragments, shed from the cell surface, have potent immunosuppressive activity and may protect tumor cells from host immune surveillance. In spite of these important functions, little is known about the transcriptional control of MUC1 gene expression or the enzymes that mediate MUC1 release, in any system. Thus, fundamental information on the mechanisms of MUC1 gene regulation and MUC1 removal or release is needed. This knowledge should provide new, rational approaches to modulate MUC1 expression to achieve desired goals, e.g., enhancement of MUC1 expression to improve epithelial barrier function during infection or reduction in MUC1 expression to improve implantation success and tumor therapies.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project--Cooperative Agreements (U01)
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Reproductive Biology Study Section (REB)
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Tasca, Richard J
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University of Delaware
Schools of Arts and Sciences
United States
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Julian, Joanne; Dharmaraj, Neeraja; Carson, Daniel D (2009) MUC1 is a substrate for gamma-secretase. J Cell Biochem 108:802-15
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Al-Shami, Rania; Sorensen, Esben S; Ek-Rylander, Barbro et al. (2005) Phosphorylated osteopontin promotes migration of human choriocarcinoma cells via a p70 S6 kinase-dependent pathway. J Cell Biochem 94:1218-33
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Brayman, Melissa; Thathiah, Amantha; Carson, Daniel D (2004) MUC1: a multifunctional cell surface component of reproductive tissue epithelia. Reprod Biol Endocrinol 2:4

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