Bcl-xL gain of function and p19 ARF loss of function cooperate oncogenically with Myc in vivo by distinct mechanisms

Cancer Cell. 2006 Aug;10(2):113-20. doi: 10.1016/j.ccr.2006.06.017.


Overexpression of Bcl-xL, loss of p19 ARF, and loss of p53 all accelerate Myc oncogenesis. All three lesions are implicated in suppressing Myc-induced apoptosis, suggesting that this is a common mechanism by which they synergize with Myc. However, using an acutely switchable model of Myc-induced tumorigenesis, we demonstrate that each lesion cooperates with Myc in vivo by a distinct mechanism. While Bcl-xL blocks Myc-induced apoptosis, inactivation of p19 ARF enhances it. However, this increase in apoptosis is matched by increased Myc-induced proliferation. p53 inactivation shares features of both lesions, partially suppressing apoptosis while augmenting proliferation. Bcl-xL and p19 ARF loss together synergize to further accelerate Myc oncogenesis. Thus, differing lesions cooperate oncogenically with Myc by discrete mechanisms that can themselves synergize with each other.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Proliferation
  • Cell Transformation, Neoplastic*
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Genes, myc / physiology*
  • Insulin-Secreting Cells / pathology
  • Mice
  • Mice, Transgenic
  • Tumor Suppressor Protein p14ARF / physiology*
  • Tumor Suppressor Protein p53 / physiology
  • bcl-X Protein / physiology*


  • Bcl2l1 protein, mouse
  • Cdkn1a protein, mouse
  • Cdkn2a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Tumor Suppressor Protein p14ARF
  • Tumor Suppressor Protein p53
  • bcl-X Protein