2 DISTINCT TARGET-CELLS FOR V-JUN MEDIATED WOUND TUMORIGENESIS

Citation
F. Shalaby et al., 2 DISTINCT TARGET-CELLS FOR V-JUN MEDIATED WOUND TUMORIGENESIS, Oncogene, 9(9), 1994, pp. 2579-2588
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Genetics & Heredity",Oncology
Journal title
ISSN journal
0950-9232
Volume
9
Issue
9
Year of publication
1994
Pages
2579 - 2588
Database
ISI
SICI code
0950-9232(1994)9:9<2579:2DTFVM>2.0.ZU;2-3
Abstract
Transgenic mice expressing v-jun under the control of the H-2K promote r develop dermal fibrosarcomas and rhabdomyosarcomas via a multistep p rocess following wounding. To assess the relative roles that wounding and the H-2K promoter play in this process, we compared the phenotype of H-2K-v-jun mice with that of animals expressing v-jun under the con trol of the metallothionein I (MTI) promoter. MT-v-jun animals also de velop wound-induced neoplasms by a multistage process. Both early and late features of tumorigenesis in MT-v-jun mice are different, however , from what is observed in H-2K-v-jun animals. First, the acute hyperp lastic response that is characteristic of H-2K-v-jun granulation tissu e is not observed in MT-v-jun wounds. Second, the myogenic components that are readily detected in the majority of late stage H-2K neoplasms are never observed in their MT counterparts. Moreover, analysis of wo und tumours arising in animals expressing both MT-v-jun and H-2K-v-jun reveals that the two transgenes are not expressed in identical malign ant cell populations. These results imply that mesenchymal granulation tissue is heterogeneous in composition and that the different cellula r phenotypes of MT-v-jun and H-2K-v-jun malignancies result from oncog enic activation of wound-derived cells which differ in their different iation potential. Thus, whereas the wounding component of multistage t umorigenesis is attributable to the action of v-jun, the transcription al regulatory elements which drive its expression determine the nature of the target cells which give rise to wound-induced neoplasms.