Differential transformation of primary human embryo retinal cells by adenovirus E1 regions and combinations of E1A + ras.
The efficiency of transformation of primary human embryo retinal (HER) cells by the adenovirus E1 region (E1A + E1B) depended on the virus serotype whereas transformation by E1A alone was a rare event regardless of serotype. Activated human c-Ha-ras and N-ras genes co-operated differentially with different E1As for HER transformation but were ineffective without E1A. Ras + E1A co-transformants containing Ad 12 E1A established directly from foci, in contrast to those containing Ad 2 or Ad 5 E1A. A spectrum of activated ras gene expression was found in stable co-transformants with mRNA and protein levels being lower in Ad 12 E1A + N-ras than Ad 2 E1A + N-ras cell lines. Down regulation of E1A transcription in the absence of E1B was found in Ad 2 E1A + Ha-ras transformants only but E1A protein levels were similar to those in Ad 2 E1A + N-ras or Ad 5 E1A + E1B cell lines. HER cell transformants which contained Ad 12 E1A were more tumourigenic than those which contained the Ad 2 or Ad 5 E1A. This unique transformation system shows that stable malignant transformation of primary human cells in vitro is a complex process requiring the combined activities of two or more types of genes.
Byrd
P J
PJ
Department of Cancer Studies, Medical School, Birmingham, UK.
Grand
R J
RJ
Gallimore
P H
PH
D017456:Adenovirus Early Proteins; D000260:Adenoviruses, Human / Q000235:genetics* / Q000276:immunology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D011905:Genes, ras; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012160:Retina / Q000166:cytology; D012703:Serotyping; D014158:Transcription, Genetic
D017456:Adenovirus Early Proteins; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins