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 E1a is a tumor suppressor gene in certain human cell lines. In the present report, I demonstrate that E1a 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. E1a 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 E1a's tumor suppression activity, possibly through sensitization to anoikis (Frisch, S.M., and H. Francis, 1994. J. Cell Biol. 124:619-626).
Frisch
S M
SM
La Jolla Cancer Research Foundation, La Jolla, California 92037.
D017500:Adenovirus E1A Proteins / Q000096:biosynthesis / Q000502:physiology*; D015152:Blotting, Northern; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D004553:Electric Conductivity; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology / Q000648:ultrastructure; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D015870:Gene Expression; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D007633:Keratins / Q000096:biosynthesis / Q000502:physiology; D008854:Microscopy, Electron; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D007633:Keratins