Expression of CCAAT/enhancer binding proteins (C/EBP) is associated with squamous differentiation in epidermis and isolated primary keratinocytes and is altered in skin neoplasms.
The epidermis is a stratified squamous epithelium composed primarily of keratinocytes that undergo sequential changes in gene expression during differentiation. CCAAT/enhancer binding proteins (C/EBP) are members of the bZIP family of DNA binding proteins/transcription factors. Northern analysis demonstrated that C/EBPalpha, C/EBPbeta, and C/EBPdelta mRNA are expressed in mouse epidermis and their mRNA levels were generally greater than those observed in other tissues known to express high levels of C/EBP. Western analysis of isolated epidermal cell nuclei demonstrated the presence of a 42 and 30 kDa C/EBPalpha protein and 35 kDa C/EBPbeta protein. Immunohistochemical localization of C/EBPalpha and C/EBPbeta in intact interfollicular epidermis revealed that C/EBPbeta expression is exclusive to the nuclei of a three-cell cluster of suprabasal keratinocytes that is morphologically consistent with the central column of the epidermal proliferative unit, and that C/EBPalpha is expressed in the nuclei and cytoplasm of suprabasal keratinocytes and weakly expressed in a perinuclear manner in some basal keratinocytes. In squamous cell carcinomas the expression of C/EBPalpha and C/EBPbeta was greatly diminished as both the intensity of nuclear staining and the number of cells expressing C/EBPalpha and C/EBPbeta were reduced. In isolated primary mouse keratinocytes, calcium-induced differentiation was accompanied by specific temporal changes in the expression of C/EBPalpha, C/EBPbeta, and C/EBPdelta mRNA and C/EBPalpha and C/EBPbeta protein. These results implicate a role for the C/EBP family in the regulation of genes involved in or specifically expressed during the process of squamous differentiation in epidermis.
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Molecular and Cellular Toxicology, Department of Toxicology, North Carolina State University, Raleigh 27695-7633, USA.
Smart
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D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000737:chemistry; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D011247:Pregnancy; D012867:Skin / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D012878:Skin Neoplasms / Q000737:chemistry* / Q000378:metabolism; D013347:Subcellular Fractions / Q000737:chemistry; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D002118:Calcium