Two distinct target cells for v-jun mediated wound tumorigenesis.
Transgenic mice expressing v-jun under the control of the H-2K promoter develop dermal fibrosarcomas and rhabdomyosarcomas via a multistep process 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 control of the metallothionein I (MTI) promoter. MT-v-jun animals also develop 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 hyperplastic response that is characteristic of H-2K-v-jun granulation tissue 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 wound tumours arising in animals expressing both MT-v-jun and H-2K-v-jun reveals that the two transgenes are not expressed in identical malignant cell populations. These results imply that mesenchymal granulation tissue is heterogeneous in composition and that the different cellular phenotypes of MT-v-jun and H-2K-v-jun malignancies result from oncogenic activation of wound-derived cells which differ in their differentiation potential. Thus, whereas the wounding component of multistage tumorigenesis is attributable to the action of v-jun, the transcriptional regulatory elements which drive its expression determine the nature of the target cells which give rise to wound-induced neoplasms.
Shalaby
F
F
Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Schuh
A C
AC
Breitman
M L
ML
D000818:Animals; D015870:Gene Expression; D016758:Genes, jun; D006183:H-2 Antigens / Q000235:genetics; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009132:Muscles / Q000378:metabolism; D012513:Sarcoma, Experimental / Q000209:etiology*; D012878:Skin Neoplasms / Q000209:etiology*; D014407:Tumor Cells, Cultured; D014947:Wounds and Injuries / Q000150:complications*
D006183:H-2 Antigens; D008668:Metallothionein