Claudins: unlocking the code to tight junction function during embryogenesis and in disease.
ABSTRACT Claudins are the structural and molecular building blocks of tight junctions. Individual cells express more than one claudin family member, which suggests that a combinatorial claudin code that imparts flexibility and dynamic regulation of tight junction function could exist. Although we have learned much from manipulating claudin expression and function in cell lines, loss-of-function and gain-of-function experiments in animal model systems are essential for understanding how claudin-based boundaries function in the context of a living embryo and/or tissue. These in vivo manipulations have pointed to roles for claudins in maintaining the epithelial integrity of cell layers, establishing micro-environments and contributing to the overall shape of an embryo or tissue. In addition, loss-of-function mutations in combination with the characterization of mutations in human disease have demonstrated the importance of claudins in regulating paracellular transport of solutes and water during normal physiological states. In this review, we will discuss specific examples of in vivo studies that illustrate the function of claudin family members during development and in disease.
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ABSTRACT: Our understanding of the essential role played by cancer stem cells or tumor-initiating cells in epithelial cell-derived tumor types is rapidly advancing. Nevertheless, the identification and characterization of these cells pose a considerable challenge. Among changes in the epithelium in oncogenesis are changes in the permeability barrier, a phenotypic trait based on tight junction formation and function. Tight junctions regulate the movement of solutes, ions and water across the paracellular space. On a cellular level, they maintain cell polarity by limiting the lateral diffusion of membrane components. Depending on the type of epithelial tissue, the barrier characteristics with respect to electrical resistance, size and ion charge selectivity vary quite significantly. Thus, elucidating changes in expression of Claudins, an essential component of tight junctions, has become a very active area of investigation in oncogenesis. This chapter provides detailed protocols on how to quantify three aspects of tight junction physiology using in vitro cell culture systems that are particularly applicable to analysis and comparison of cancer stem cells and their normal counterparts.Stem cell reviews 12/2011; 8(3):1030-4. · 5.08 Impact Factor
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ABSTRACT: Recent studies suggest that the poorer breast cancer outcome observed in African-American women (AAW) may, in part, result from underlying molecular factors. The purpose of this study was to investigate gene expression differences between Caucasian-American women (CAW) and AAW that may contribute to this poorer prognosis. The expression of 84 genes involved in breast carcinoma prognosis, response to therapy, estrogen signaling, and tumor aggressiveness was assessed in age- and stage-matched CAW and AAW paraffin-embedded breast cancer specimens. The Wilcoxon-Mann-Whitney Test was used to identify genes with a significant difference in expression between CAW and AAW. To determine if the differentially expressed genes could segregate between the CAW and AAW, we performed semi-supervised principal component analysis (SSPCA). Twenty genes were differentially expressed between AAW and CAW. SSPCA incorporating these 20 genes segregated AAW and CAW into two distinct groups. AAW were significantly (p < 0.05) more likely to display aberrations in G1/S cell-cycle regulatory genes, decreased expression of cell-adhesion genes, and low to no expression of ESR1, PGR, ERBB2 and estrogen pathway targets. The gene expression differences identified between AAW and CAW may contribute to more aggressive disease, resistance to therapy, enhanced metastatic potential and poor clinical outcome. These findings support the hypothesis that breast cancer specimens collected from AAW display distinct gene expression differences compared to similar tissues obtained from CAW. Additional population-based studies are necessary to determine if these gene expression variations contribute to the highly aggressive and treatment-resistant breast cancer phenotype frequently observed in AAW.BMC Research Notes 05/2012; 5:248.
- Developmental Biology - DEVELOP BIOL. 01/2011; 356(1):169-169.