Obligatory wounding requirement for tumorigenesis in v-jun transgenic mice

Nature. 1990 Aug 23;346(6286):756-60. doi: 10.1038/346756a0.


Avian sarcoma virus 17 induces fibrosarcomas in chickens and can transform a number of avian cell types in vitro by the action of v-jun. This gene and the related cellular genes c-jun, jun B and jun D, encode transactivating (or repressing) DNA-binding proteins that form homo- or heterodimeric (Jun-Jun and Jun-Fos) complexes which recognize the AP-1 consensus sequence TGACTCA, a response element that confers sensitivity to the tumour-promoting phorbol ester TPA. We have produced several lines of transgenic mice carrying the v-jun oncogene, driven by the promoter of the widely expressed H-2KK major histocompatibility complex (MHC) class I antigen gene. Transgenic animals are initially phenotypically normal, but after full-thickness wounding they show abnormal wound repair, characterized by hyperplastic granulation tissue. Many of these lesions are slowly progressive because of continuing fibroblast proliferation, and over 2-5 months some give rise to dermal fibrosarcomas. This reproducible multistep transition through a proliferative but benign intermediate is associated with characteristic increments in v-jun expression. Moreover, hyperplastic wound repair and its progression are both related to transgene dosage, suggesting that there exists a quantitative requirement or threshold for v-jun action. Our results indicate that v-jun is not oncogenic in transgenic mice as a result of a 'single-hit' mechanism, but rather, in addition to an obligatory wound, that secondary genetic or epigenetic events (possibly conscripting normal constituents of wound repair) are necessary for tumour development and progression.

Publication types

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

MeSH terms

  • Animals
  • Avian Sarcoma Viruses / genetics
  • Blotting, Northern
  • Cell Line
  • Fibrosarcoma / genetics*
  • Fibrosarcoma / pathology
  • Genes, MHC Class I
  • Mice
  • Mice, Transgenic
  • Oncogene Protein p65(gag-jun)
  • Oncogenes*
  • Protein-Tyrosine Kinases / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / isolation & purification
  • Retroviridae Proteins, Oncogenic / genetics*
  • Transcription, Genetic
  • Wounds and Injuries / pathology*


  • Oncogene Protein p65(gag-jun)
  • RNA, Messenger
  • Retroviridae Proteins, Oncogenic
  • Protein-Tyrosine Kinases