title: Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation.
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.
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006657:Histones / Q000235:genetics; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009857:Oncogenes
chemical_list: D000199:Actins; D006657:Histones