Ras-mediated cell cycle arrest is altered by nuclear oncogenes to induce Schwann cell transformation

EMBO J. 1988 Jun;7(6):1635-45.

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

  • Animals
  • Antigens, Polyomavirus Transforming / physiology*
  • Cell Cycle
  • Cell Division
  • Cell Nucleus
  • Cell Transformation, Neoplastic* / pathology*
  • Cell Transformation, Viral*
  • Cells, Cultured
  • Growth Substances / pharmacology
  • Oncogene Protein p21(ras)
  • Oncogene Proteins, Viral / physiology*
  • Oncogenes*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-myc
  • Rats
  • Rats, Inbred Strains
  • Schwann Cells / pathology*

Substances

  • Antigens, Polyomavirus Transforming
  • Growth Substances
  • Oncogene Proteins, Viral
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myc
  • Oncogene Protein p21(ras)