Myc drives apoptosis in PC12 cells in the absence of Max

Oncogene. 2001 Jun 21;20(28):3746-50. doi: 10.1038/sj.onc.1204466.

Abstract

A conditionally active chimeric form of the c-Myc protein fused to the ligand-binding domain of the estrogen receptor (MycER) was expressed in PC12 cells. Induction of Myc activity resulted in a threefold increase in apoptosis after 5 days when cells were maintained in 1% serum. The effect of Myc overexpression was dependent on its DNA-binding domain but not on its heterodimeric binding protein Max, which is absent in PC12 cells. Preincubation of the c-Myc overexpressing cells with either NGF or bFGF, but not EGF, prevented the Myc-mediated increase in apoptosis, although the signaling pathways used by NGF and bFGF to block cell death differed. NGF-mediated rescue was mediated by the phosphatidylinositol 3'-OH (P13) kinase/Akt pathway while rescue by bFGF was not affected by P13 kinase inhibitors. These results show that Myc can induce apoptosis in PC12 cells in a Max-independent manner and that alternate signaling pathways exist to mediate cell survival.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins / metabolism*
  • Epidermal Growth Factor / metabolism
  • Fibroblast Growth Factor 2 / metabolism
  • Nerve Growth Factor / metabolism
  • PC12 Cells
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transcription Factors*

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • Max protein, rat
  • Myc associated factor X
  • Proto-Oncogene Proteins c-myc
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor
  • Nerve Growth Factor