Chapter 4 The Experimental Manipulation of Keratin Expression and Organization in Epithelial Cells and Somatic Cell Hybrids

Abstract

Keratins are found in nearly all epithelial tissue types in vertebrates, and in many cases keratins constitute the majority of the proteins produced ( for e.g., skin and its derivatives). Their organization in the cytoplasm of epithelial cells has made them the fundamental elements of the cytoskeleton and established them as a part of a much larger, interrelated group of polymer-forming proteins that give rise to intermediate filaments. Experimental manipulation of epithelial cells provides a means by which these proteins and the filaments formed by them can be better understood, both in the context of basic cell biology and with regard to their importance in the clinical diagnosis of disease. This chapter discusses some of the consequences of the cytological and genetic manipulation of keratin intermediate filaments in epithelial cells and somatic cell hybrids. The approaches presented are used to investigate keratin intermediate filaments with respect to the overall structure and function of the vertebrate cytoskeleton and to relate the expression of keratin genes and the subsequent organization of keratins to specific cell behavior and growth potential. Results and interpretations from two experimental approaches are presented in the chapter in which the expression and/or organization of keratins has been altered. The first involves the analysis of drug-induced alterations of cytokeratin in cultured epithelial cells and the second focuses on the analysis of clonal variations in keratin filament expression by human somatic cell hybrids.