Obligatory wounding requirement for tumorigenesis in v-jun transgenic mice View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1990-08

AUTHORS

A C Schuh, S J Keating, F S Monteclaro, P K Vogt, M L Breitman

ABSTRACT

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. More... »

PAGES

756

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/346756a0

DOI

http://dx.doi.org/10.1038/346756a0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042345364

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/2167455


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