FBXW7 inactivation in a BrafV600E -driven mouse model leads to melanoma development

Pigment Cell Melanoma Res. 2017 Jan;30(6):571-574. doi: 10.1111/pcmr.12603. Epub 2017 Jul 4.

Abstract

Human melanocytic nevi driven by BRAFV600E are in a growth-arrested state referred as oncogene-induced senescence. FBXW7 tumor suppressor is mutated in melanomas, but not in benign precursor melanocytic nevi. In order to characterize whether inactivation of FBXW7 in cooperation with BRAFV600E (BrafV637E in the mouse) is sufficient to bypass from the growth-arrested state, we generated a murine model by conditionally silencing Fbxw7 in an established system, Tyr::CreER; BrafCA (or Tyr::CreER; BrafV600E). We show that loss of Fbxw7 in the presence of BrafV600E mutation is consequential and sufficient to drive tumorigenesis. This model provides further evidence that Fbxw7 is a tumor suppressor in the melanocytic lineage, and can serve as a tool for future pre-clinical studies.

Publication types

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

MeSH terms

  • Animals
  • Disease Models, Animal*
  • F-Box-WD Repeat-Containing Protein 7 / physiology*
  • Humans
  • Melanoma, Experimental / etiology
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology*
  • Mice
  • Mutation*
  • Proto-Oncogene Proteins B-raf / genetics*

Substances

  • F-Box-WD Repeat-Containing Protein 7
  • Fbxw7 protein, mouse
  • Braf protein, mouse
  • Proto-Oncogene Proteins B-raf