Immortalization of rat embryo fibroblasts by the cellular p53 oncogene.
Intact and rearranged p53 genes from Friend virus-induced erythroleukemic cell lines which code for proteins of 53- (p53) and 44-kDa (p44), respectively, were cloned into pUC18 and tested for their ability to immortalize rat embryo fibroblasts. The functional p53 gene from normal Balb/c mouse liver was also tested for immortalizing activity. Immortal cells were obtained with the three genes although the efficiency of immortalization by p44 was lower than that by p53. Expression of murine p53 and p44 in the established rat cell lines was confirmed by metabolic labeling and Western Blotting. Our results demonstrate that elevated expression of the mouse p53 gene, driven by its natural promoter and in the absence of strong heterologous promoters and/or enhancers, can efficiently immortalize early-passage rat embryo fibroblasts. p53-immortalized cells but not p44-immortalized cells could be morphologically transformed by secondary transfection with activated Ha-ras. Thus 5'-coding sequences of the p53 gene appear necessary for ras complementation but not for immortalization.
Rovinski
B
B
Division of Biological Research, Ontario Cancer Institute, Toronto, Canada.
Benchimol
S
S
D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000235:genetics; D005786:Gene Expression Regulation; D005796:Genes; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics; D051379:Mice; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000502:physiology*; D009374:Neoplasms, Experimental / Q000235:genetics; D010750:Phosphoproteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051381:Rats; D013329:Structure-Activity Relationship; D014162:Transfection; D016159:Tumor Suppressor Protein p53
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53