Keratinocyte differentiation markers: involucrin, transglutaminase, and toxicity

Studies of three keratinocyte differentiation markers are described. First, the involucrins of several mammals are identified, facilitating use of this marker in animal models of human disease. The rapid evolution of involucrin has prevented its routine immunochemical identification beyond the primates, but its unusual solubility and its labeling by transglutaminase have permitted detection in rats, cats, and sheep. Second, the re-expression of keratinocyte transglutaminase in carcinoma cells lacking the enzyme is demonstrated. Lack of this enzyme expression has been observed previously in squamous cell carcinomas. The present finding suggests genomic hypermethylation could contribute to this phenomenon and offers an approach to analyzing transcriptional features of the enzyme regulation. Third, the sensitivity of keratinocytes to growth suppression by aflatoxin B1 is reported. The observed toxicity appears to be mediated by aryl hydrocarbon hydroxylase, a metabolic enzyme inducible in keratinocytes by environmental agents. Such expression may be relevant to carcinogenesis in tissues subject to squamous metaplasia as well as in other exposed cell types stimulated to express this biotransformation enzyme.