EXPRESSION PATTERN OF THE CELL-ADHESION MOLECULES E-CADHERIN, P-CADHERIN AND ALPHA-6-BETA-3 INTEGRIN IS ALTERED IN PREMALIGNANT SKIN TUMORSOF P53-DEFICIENT MICE

Expression of the cell adhesion molecules E-cadherin, P-cadherin and ( alpha 6 beta 4 integrin and of the keratin K13 has been analyzed in ch emically induced benign skin papillomas with genetically pre-determine d risks for malignant conversion. It has been previously shown that pa pillomas induced in mice lacking both alleles of the p53 gene have a m uch higher rate of malignant conversion than those induced in wild-typ e and heterozygous p53 mice. Alterations in the expression pattern of the E-cadherin molecule, including focal loss at cell-cell contacts an d heterogeneous distribution in the differentiated layers, were found in about 70% of the p53 null papillomas. In contrast, all of the wild- type and over 85% of the heterozygous p53 papillomas exhibited an expr ession pattern of E-cadherin indistinguishable from that of normal epi dermis. Alterations in P-cadherin expression were also detected in the p53 null papillomas: aberrant suprabasal localization and heterogeneo us distribution were observed more frequently than in heterozygous and wild-type p53 papillomas. The alpha 6 beta 4 integrin showed suprabas al expression in move than 70% of the papillomas derived from either w ild-type, heterozygous or homozygous p53 null mice. Surprisingly, the extent of the suprabasal localization of alpha 6 beta 4 decreased in t he p53 null papillomas. Aberrant keratin K13 expression was also detec ted in the majority of cases of all p53 genotypes, but again there was a clear decrease in expression levels in the p53 null papillomas. The se alterations were also associated with keratinocytic atypia, which i ncreased significantly in the p53 null papillomas. Changes in these pa rameters were particularly evident during malignant conversion in inva sive regions of one progressing p53 null papilloma. Our results indica te the existence of dynamic changes in the expression pattern of the 3 cell adhesion molecules analyzed and identify down-regulation of E-ca dherin as an early step in malignant conversion. (C) 1996 Wiley-Liss, Inc.