Temporal alterations in cytokeratin expression during experimental oral mucosal carcinogenesis

Precancerous lesions and squamous cell carcinomas (SCCs) were induced in the oral mucosa of outbred male Sprague-Dawley rats by repeated application of the carcinogen 4-nitroquinoline-1-oxide. Temporal alterations in the pattern of cytokeratins expressed by epithelial cells in these developing neoplasms were investigated by means of one- and two-dimensional polyacrylamide gel electrophoresis and by probing electrophoretic blots of these gels with anticytokeratin antibodies. Progressive diminution in the expression of a 58.3 kDa cytokeratin was detected in moderately dysplastic epithelium and subsequent lesions, as was reduced expression of a 53.5 kDa cytokeratin after a stage of severe dysplasia had been induced. Analysis of two-dimensional electrophoretograms indicated an alkaline shift of acidic variants of a 49.0 kDa cytokeratin in moderately dysplastic epithelium; this shift was more pronounced in the induced, severely dysplastic epithelium and SCCs. The latter finding of an alkaline shift in cytokeratins of dysplastic epithelial cells has not been previously reported in preneoplastic lesions.