title: Ras-mediated cell cycle arrest is altered by nuclear oncogenes to induce Schwann cell transformation.
abstract: The cellular responses to ras and nuclear oncogenes were investigated in purified populations of rat Schwann cells. v-Ha-ras and SV40 large T cooperate to transform Schwann cells, inducing growth in soft agar and allowing proliferation in the absence of added mitogens. Expression of large T alone reduces their growth factor requirements but is insufficient to induce full transformation. In contrast, expression of v-Ha-ras leads to proliferation arrest in Schwann cells expressing a temperature-sensitive mutant of large T at the restrictive temperature. Cells arrest in either the G1 or G2/M phases of the cell cycle, and can re-enter cell division at the permissive temperature even after prolonged periods at the restrictive conditions. Oncogenic ras proteins also inhibit DNA synthesis when microinjected into Schwann cells. Adenovirus E1a and c-myc oncogenes behave similarly to SV40 large T. They cooperate with Ha-ras oncogenes to transform Schwann cells, and prevent ras-induced growth arrest. Thus nuclear oncogenes fundamentally alter the response of Schwann cells to a ras oncogene from cell cycle arrest to transformation.
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D002453:Cell Cycle; D002455:Cell Division; D002467:Cell Nucleus; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D006133:Growth Substances / Q000494:pharmacology; D015689:Oncogene Protein p21(ras); D009856:Oncogene Proteins, Viral / Q000502:physiology*; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc; D051381:Rats; D011919:Rats, Inbred Strains; D012583:Schwann Cells / Q000473:pathology*
chemical_list: D000952:Antigens, Polyomavirus Transforming; D006133:Growth Substances; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D015689:Oncogene Protein p21(ras)