Cessation of cytokeratin expression in a rat hepatoma cell line lacking differentiated functions

Abstract

Intermediate-sized filaments (IF) of diameter 7–11 nm occur in the cytoplasm of most cells of vertebrates and their constituent proteins are abundant in most cell types. Expression of IF proteins depends on the route of cell differentiation and five major subclasses of IF proteins have been distinguished^1–5: of these, cytokeratins are typical of epithelial cells whereas vimentin occurs in mesenchymally derived cells and some other non-epithelial cells. When epithelial cells are grown in culture this restriction of IF expression is often lost and they begin to synthesize vimentin in addition to cytokeratin^5–9, although examples of maintenance of the cell-type-specific expression of only cytokeratin have also been reported^8,10. No IFs have been detected in mammalian germ cells or in pre-morula stages of mouse embryogenesis, and the first IF proteins identified in murine blastocysts are cytokeratins of trophectodermal cells^11,12. We report here that a dedifferentiated¹³ rat hepatoma cell clone, which has become resistant to the action of the glucocorticoid hormone analogue dexamethasone and has lost various liver-specific functions, also stops all synthesis of IF proteins, without obvious consequences for growth and proliferation. The existence of such cells devoid of IF supports the notion that such filaments are not involved in basic cellular functions necessary for growth and proliferation but are related to special functions of the differentiated cell.