Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation

Cell. 1984 Feb;36(2):241-7. doi: 10.1016/0092-8674(84)90217-4.

Abstract

Cellular oncogenes are DNA sequences implicated in the genesis of cancer, but their functions in the transformation process are not understood. Our experiments provide data linking expression of two well-studied proto-oncogenes, c-myc and c-rasKi, to current knowledge of proliferation control and its perturbation by differentiation and chemical transformation. Growth stimulation of quiescent cells by serum elevates expression of the myc proto-oncogene in Balb/c 3T3 (A31) cells. In two chemically transformed A31 derivatives (BPA31 and DA31), c-myc expression is constitutive. The levels of c-myc mRNA in quiescent and growing transformed cells are nearly the same, and are only slightly elevated compared to the level found in growing A31 cells. By contrast, c-rasKi expression is cell-cycle-dependent in BPA31 cells. The relative abundance of c-rasKi mRNA begins to increase in mid- to late G0/G1. During terminal differentiation of teratocarcinoma stem cells (F9) into nonproliferating endoderm, relative mRNA abundance is diminished more markedly for c-myc than for c-rasKi. These results demonstrate that expression of the myc and rasKi proto-oncogenes is dependent upon the cellular growth state, and that growth control exhibits growth-factor-dependent, cell-cycle-timed oncogene expression. In the case of the BPA31 cells, c-myc is not rearranged, amplified, or overexpressed. However, the oncogene has lost its cycle-dependent regulation in the chemically transformed cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / genetics
  • Animals
  • Cell Cycle*
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Histones / genetics
  • Kinetics
  • Mice
  • Mice, Inbred BALB C
  • Oncogenes*

Substances

  • Actins
  • Histones