MUC1: A multifunctional cell surface component of reproductive tissue epithelia
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BioMed Central
Open Access
Review
MUC1: A multifunctional cell surface component of reproductive tissue epithelia Melissa Brayman, Amantha Thathiah and Daniel D Carson* Address: Department of Biological Sciences, University of Delaware, Newark, DE USA 19716 Email: Melissa Brayman - [email protected]; Amantha Thathiah - [email protected]; Daniel D Carson* - [email protected] * Corresponding author
Published: 07 January 2004 Reproductive Biology and Endocrinology 2004, 2:4
Received: 06 October 2003 Accepted: 07 January 2004
This article is available from: http://www.rbej.com/content/2/1/4 © 2004 Brayman et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
Abstract MUC1 is a large, transmembrane mucin glycoprotein expressed at the apical surface of a variety of reproductive tract epithelia. Functions attributed to MUC1 include those generally associated with mucins such as lubrication and hydration of cell surfaces as well as protection from microorganisms and degradative enzymes. In addition, MUC1 is an effective inhibitor of both cell-cell and cellextracellular matrix interactions in both normal and malignant contexts. Moreover, a series of recent studies has shown that the highly conserved cytoplasmic tail of MUC1 interacts specifically with a series of important signal transducing molecules including β-catenin, Grb2 and erbB family members. MUC1 expression in normal epithelia can be quite dynamic, varying in response to steroid hormone or cytokine influences. Following malignant transformation, MUC1 often becomes highly overexpressed, loses its apical restriction, and displays aberrant glycosylation and altered mRNA splice variants. Regulation of MUC1 expression can occur at the transcriptional level. In addition, post-translational regulation of cell surface expression occurs via the activity of cell surface proteases or "sheddases" that release soluble forms of the large ectodomains. This review will briefly summarize studies of MUC1 expression and function in reproductive tissues with particular emphasis on the uterus. In addition, current knowledge of the mechanisms of MUC1 gene regulation, metabolic processing and potential signal transducing functions will be presented.
MUC1 structure and expression The MUC1 gene encodes a type-I transmembrane glycoprotein that is expressed on the apical surface of most simple epithelia, including mammary gland, female reproductive tract, lung, kidney, stomach, gall bladder, and pancreas as well as some non-epithelial cell types [reviewed in [1]]. The human MUC1 gene spans 4 to 7 kb and is comprised of 7 exons that can be alternatively spliced to form transcripts from 3.7 to 6.4 kb. The fulllength protein contains three domains: short cytoplasmic and transmembrane domains that are highly conserved among species, and a large extracellular domain (Fig. 1). The extracellular domain in humans
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