Dominant negative MYC blocks transformation by ABL oncogenes

C L Sawyers1, W Callahan, O N Witte

  • 1Department of Medicine, Howard Hughes Medical Institute, University of California, Los Angeles 90024.

Cell
|September 18, 1992
PubMed

Insights

High MYC levels synergize with ABL oncogenes. Dominant-negative MYC suppressed ABL-induced transformation, demonstrating c-MYC

Area of Science:

  • Oncogenomics
  • Cellular Transformation
  • Molecular Biology

Background:

  • MYC oncogene expression often synergizes with ABL oncogenes.
  • The precise role of MYC in ABL-mediated transformation requires further elucidation.

Purpose of the Study:

  • To investigate whether MYC is essential for ABL oncogene-driven cellular transformation.
  • To determine if MYC complements or is indispensable for ABL oncogene transformation.

Main Methods:

  • Overexpression of dominant-negative MYC proteins in fibroblasts.
  • Assessing the impact of dominant-negative MYC on transformation induced by v-abl and BCR-ABL oncogenes.
  • Evaluating transformation of primary mouse bone marrow pre-B cells using retroviral constructs co-expressing BCR-ABL and MYC.

Main Results:

  • Dominant-negative MYC reduced transformation by v-abl and BCR-ABL oncogenes 5- to 10-fold.
  • Transformation induced by the serine/threonine kinase oncogene v-mos remained unaffected.
  • Dominant-negative MYC suppressed BCR-ABL-mediated transformation of primary mouse bone marrow pre-B cells.

Conclusions:

  • c-MYC is essential for ABL oncogene-mediated cellular transformation.
  • These findings help define the molecular pathway involving MYC and ABL in oncogenesis.

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