Rescue of cells from ras oncogene-induced growth arrest by a second, complementing, oncogene.
Established REF52 cells (rat embryo fibroblasts) completely resist stable transformation by ras oncogenes, and simian virus 40 large tumor (T) antigen collaborates with ras to convert REF52 cells to tumorigenic state. A temperature-sensitive simian virus 40 large T antigen (encoded by tsA58) allowed the T24 Ha-ras oncogene to transform REF52 cells in a temperature-dependent manner. Two thirds of the clones transformed with tsA58 and ras became arrested in G2 or late S phase when shifted to a nonpermissive temperature for T antigen stability. Thus, ras induced growth arrest rather than stable transformation in the absence of a functional collaborating oncogene. These results indicate that collaborating oncogenes can regulate cellular responses to ras and have implications regarding therapeutic strategies to control tumor cells expressing activated ras oncogenes.
Hirakawa
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Central Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.
Ruley
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D000818:Animals; D000957:Antigens, Viral, Tumor / Q000502:physiology*; D002453:Cell Cycle; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D019204:GTP-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051381:Rats; D013539:Simian virus 40; D014162:Transfection
D000957:Antigens, Viral, Tumor; D011518:Proto-Oncogene Proteins; D019204:GTP-Binding Proteins