The esophagus is lined by a stratified squamous epithelium that is composed of proliferating basal cells and differentiated squamous cells. Basal cells undergo terminal differentiation by a series of morphological and biochemical changes which culminates in the production of squamous cells. The mechanism that controls the balance between proliferation and differentiation in the esophageal epithelium is not understood. The investigator recently developed a transgenic mouse model in which an Epstein-Barr virus promoter was fused to cyclin D1 and which resulted in the specific expression of the transgene in the basal and suprabasal layers of the esophageal epithelium. When analyzed in esophageal cell lines by transfection experiments, a cis-regulatory element containing a CACACCT motif in the promoter appears to be critical for the promoter activity. The applicant has then identified a nuclear binding activity in esophageal cell lines which he named KSF that specifically interacts with the CACACCT motif present not only in the viral promoter but in cellular promoters that are active in the basal cells of the esophageal epithelium. The applicant therefore hypothesizes that KSF plays an important role in the regulation of expression of genes involved in the control of proliferation and differentiation of the esophageal epithelium.
Three specific aims are proposed: (1) to isolate cDNA clones encoding KSF, (2) to characterize the tissue expression of KSF, and (3) to characterize the regulation of expression of the keratin 4 promoter by KSF.
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