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 epithelial-mesenchymal differentiation. The transcription factors and signal transduction pathways involved in this differentiation are being elucidated. I have previously reported (Frisch, 1991) that adenovirus Ela is a tumor suppressor gene in certain human cell lines. In the present report, I demonstrate that Ela expression caused diverse human tumor cells (rhabdomyosarcoma, fibrosarcoma, melanoma, osteosarcoma) and fibroblasts to assume at least two of the following epithelial characteristics: (a) epithelioid morphology; (b) epithelial-type intercellular adhesion proteins localized to newly formed junctional complexes; (c) keratin-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. This effect may also contribute to Ela's tumor suppression activity, possibly through sensitization to anoikis (Frisch, S. M., and H. Francis, 1994. J. Cell Biol. 124:619-626).