Role of c-myc in the transformation of REF52 cells by viral and cellular oncogenes.
Cells of the established REF52 line completely resist stable transformation by activated ras oncogenes, apparently because expression of ras p21 above a low threshold level inhibits cell proliferation. Adenovirus E1A and simian virus 40 (SV40) large T antigen enable ras oncogenes to transform REF52 cells and therefore protect REF52 cells from ras-induced growth arrest. The present study investigated the role of c-myc in regulating the responses of REF52 cells to ras oncogenes. We report that transcriptionally activated c-myc oncogenes enabled ras to transform REF52 cells but the efficiency of transformation was 20- to 30-fold lower than with E1A. In contrast, myc and E1A were similarly active as ras collaborators when assayed on primary baby rat kidney (BRK) cells. Relative difficulties transforming REF52 celis by myc and ras did not result from a requirement to express either gene at higher levels in REF52 as compared with BRK transformants. Steady state levels of endogenous c-myc RNA were unaltered in REF52 cells transformed by ras together with c-myc, E1A or SV40 large T antigen. Furthermore, ras-induced growth arrest was not accompanied by a decline in c-myc RNA levels. These results suggest that transcriptional control of c-myc is not affected either by the anti-proliferative effects of ras or by the collaborating activities of E1A and SV40 large T antigen.
Kohl
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NE
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Ruley
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HE
D017456:Adenovirus Early Proteins; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000502:physiology; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005786:Gene Expression Regulation; D009856:Oncogene Proteins, Viral / Q000502:physiology; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051381:Rats; D013539:Simian virus 40 / Q000502:physiology; D014158:Transcription, Genetic
D017456:Adenovirus Early Proteins; D000957:Antigens, Viral, Tumor; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins