E1A INDUCES THE EXPRESSION OF EPITHELIAL CHARACTERISTICS

Cells closely resembling epithelia constitute the first specific cell type in a mammalian embryo. Many other cell types emerge via epithelia l-mesenchymal differentiation. The transcription factors and signal tr ansduction pathways involved in this differentiation are being elucida ted. I have previously reported (Frisch, 1991) that adenovirus Ela is a tumor suppressor gene in certain human cell lines. In the present re port, I demonstrate that Ela expression caused diverse human tumor cel ls (rhabdomyosarcoma, fibrosarcoma, melanoma, osteosarcoma) and fibrob lasts to assume at least two of the following epithelial characteristi cs: (a) epithelioid morphology; (b) epithelial-type intercellular adhe sion proteins localized to newly formed junctional complexes; (c) kera tin-containing intermediate filaments; and (d) down-regulation of non- epithelial genes. Ela thus appeared to partially convert diverse human tumor cells into an epithelial phenotype. This provides a new system for molecular analysis of epithelial-mesenchymal interconversions. Thi s effect may also contribute to Ela's tumor suppression activity, poss ibly through sensitization to anoikis (Frisch, S. M., and H. Francis, 1994. J. Cell Biol. 124:619-626).