Inducers of mammalian cell differentiation stimulate dome formation in a differentiated kidney epithelial cell line (MDCK).

Abstract

Cell cultures of a differentiated dog kidney epithelial cell line, MDCK, spontaneously form fluid-filled domes or hemicysts composed of numbers of cells as a manifestation of specialized epithelial transport phenomena. Addition to MDCK cells of a broad spectrum of compounds that are known as potent inducers of mammalian cell differentiation in cell culture caused a striking increase in the frequency of dome formation. Polar compounds such as N,N-dimethylformamide, dimethyl sulfoxide or hexamethylene bisacetamide stimulated increased dome formation 15-30 h after addition. Induction of domes by these compounds was prevented either by inhibitors of protein synthesis or by ouabain, cytochalasin B or vinblastine. Inhibition of DNA synthesis did not block chemical induction of domes. Other inducers were compounds of physiological occurrence such as n-butyrate or adenosine. A variety of conditions expected to elevate intracellular levels of cyclic[c]AMP also stimulated dome formation. Domes may be formed in cell culture by a form of cell differentiation under positive control by cAMP.