Reversal of malignancy by the adenovirus E1a gene.
Tumor suppressor genes such as Rb and p53 usually kill tumor cells when overexpressed ectopically. This is a consequence of their normal cell cycle regulatory functions. By contrast, the E1a gene of adenovirus, a common cold virus, converts tumor cells into viable normal cells. This has advantages for investigation and control of cancer. In particular, E1a is a master programmer of the epithelial phenotype. This provides a new tool for understanding the molecular basis of the epithelial-mesenchymal transition, and how it goes awry in cancer cells. Furthermore, epithelial cells are sensitive to a form of apoptosis - 'anoikis' - that is induced by detachment from extracellular matrix. This property confers strict anchorage-dependence. Transcriptional programming, by E1a or the formation of cell-cell junctional complexes, programs epithelial cells to be sensitive to anoikis.
Frisch
S M
SM
La Jolla Cancer Research Foundation, CA 92037, USA.
D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000502:physiology; D017209:Apoptosis; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005814:Genes, Viral; D006801:Humans; D008648:Mesoderm / Q000166:cytology; D010641:Phenotype; D014158:Transcription, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D015815:Cell Adhesion Molecules