EXPRESSION OF CCAAT ENHANCER BINDING-PROTEINS (C/EBP) IS ASSOCIATED WITH SQUAMOUS DIFFERENTIATION IN EPIDERMIS AND ISOLATED PRIMARY KERATINOCYTES AND IS ALTERED IN NEOPLASMS/

The epidermis is a stratified squamous epithelium composed primarily o f keratinocytes that undergo sequential changes in gene expression dur ing differentiation. CCAAT/enhancer binding proteins (C/EBP) are membe rs of the bZIP family of DNA binding proteins/transcription factors. N orthern analysis demonstrated that C/EBP alpha, C/EBP beta, and C/EBP delta mRNA are expressed in mouse epidermis and their mRNA levels were generally greater than those observed in other tissues known to expre ss high levels of C/EBP. Western analysis of isolated epidermal cell n uclei demonstrated the presence of a 42 and 30 kDa C/EBP alpha protein and 35 kDa C/EBP beta protein. Immunochistochemical localization of C /EBP alpha and C/EBP beta in intact interfollicular epidermis revealed that C/EBP beta expression is exclusive to the nuclei of a three-cell cluster of suprabasal keratinocytes that is morphologically consisten t with the central column of the epidermal proliferative unit, and tha t C/EBP alpha is expressed in the nuclei and cytoplasm of suprabasal k eratinocytes and weakly expressed in a perinuclear manner in some basa l keratinocytes. In squamous cell carcinomas the expression of C/EBP a lpha and C/EBP beta was greatly diminished as both the intensity of nu clear staining and the number of cells expressing C/EBP alpha and C/EB P beta were reduced. In isolated primary mouse keratinocytes, calcium- induced differentiation was accompanied by specific temporal changes i n the expression of C/EBP alpha, C/EBP beta, and C/EBP delta mRNA and C/EBP alpha and C/EBP beta protein. These results implicate a role for the C/EBP family in the regulation of genes involved in or specifical ly expressed during the process of squamous differentiation in epiderm is.