Characterization of the expression pattern of p63 alpha and delta Np63 alpha in benign and malignant oral epithelial lesions

The p53 homologue p63 is essential for ectodermal differentiation, such tha t p63-/- mice lack all squamous epithelia and teeth. The p63 gene expresses at least 6 different transcripts, but information regarding the expression , regulation and function of the different isoforms has remained sparse, du e to the lack of adequate reagents directed specifically against the indivi dual proteins, Here we characterize the expression of p63 alpha/Delta Np63 alpha in benign and malignant lesions of the oral epithelium, using a speci fic antibody raised against a peptide derived from the C-terminus of p63 al pha, which does not cross-react with p53 or the other p53 homologue, p73, B y immunohistochemical analysis, we show that these p63 isoforms are express ed in the nucleus of many cells. In normal and benign lesions, p63 alpha/De lta Np63 alpha-expressing cells are mainly found suprabasally, whereas p53- expressing cells are restricted to the basal-cell layer. By RT-PCR, we show that Delta Np63 alpha is the predominant isoform in cell lines from squamo us-cell carcinomas of the head and neck, confirming our immunochemical obse rvations, Our data are consistent with studies suggesting a role for p63 in the transit-amplifying population of epidermal cells, Over-expression of p 63 alpha, and in particular the Delta N form, was frequently seen in carcin omas. Taken together with previous analyses of p63 expression, our data sug gest distinct roles for different p63 isoforms in the regulation of growth and/or differentiation of epithelial cells. Moreover, our data are compatib le with the notion that p63 can act to promote neoplastic growth in the ora l epithelium. Int. J. Cancer 87:368-372, 2000. (C) 2000 Wiley-Liss, Inc.