EXPRESSION OF THE ANHIDROTIC ECTODERMAL DYSPLASIA GENE IS REDUCED IN SKIN-CANCER COINCIDING WITH REDUCED E-CADHERIN

X-linked anhidrotic ectodermal dysplasia (EDA) is characterized by def ects in the development of hair, teeth, and sweat glands. We have rece ntly cloned the gene for EDA by positional cloning. The EDA gene encod es a transmembrane protein with a putative role in epithelial-mesenchy mal interactions. Since EDA could play a role in cell-cell or cell-mat rix adhesion, acantholytic skin diseases and several types of non-inva sive and invasive skin cancers were studied using in situ hybridizatio n. Because of the observation that the promoter region of the EDA gene contains a binding site for LEF-1, which is involved in the signaling through E-cadherin/beta catenin complex, we compared the expression o f EDA with immunolocalization for E-cadherin (E-CD). EDA expression du ring hair growth cycle, in benign adnexal tumors, and neuroectoderm-de rived nevus cells was also examined. Our findings indicate that EDA ex pression is less abundant in malignant tumors, including basal and squ amous cell carcinomas and melanoma, and in acantholytic keratinocytes compared to normal epidermis. The reduction in expression also coincid es with diminished E-CD staining in all malignant cell types and in ac antholytic cells. Our results suggest that EDA protein functions in th e regulation of epithelial cell contacts and that it may be associated with the E-CD signaling pathway.