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Two distinct target cells for v-jun mediated wound tumorigenesis
F Shalaby1, A C Schuh, M L Breitman
1Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Oncogene
|September 1, 1994
Summary
Wounding combined with specific gene promoters can trigger cancer in mice. The promoter type influences the cancer type, indicating that wound-healing cells have varied potentials for tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Transgenic mice expressing v-jun under the H-2K promoter develop specific tumors after wounding.
- The role of the promoter in directing tumor development requires further investigation.
Purpose of the Study:
- To compare the tumor development process in mice with v-jun expression driven by the H-2K promoter versus the metallothionein I (MTI) promoter.
- To determine how transcriptional regulatory elements influence the cell types targeted for oncogenesis following wounding.
Main Methods:
- Generated and analyzed transgenic mice expressing v-jun under the H-2K and MTI promoters.
- Compared the phenotypic characteristics of wound-induced tumors in H-2K-v-jun and MT-v-jun mice.
- Analyzed transgene expression in malignant cell populations of co-expressing mice.
Main Results:
- Both H-2K-v-jun and MT-v-jun mice developed wound-induced neoplasms via a multistage process.
- MT-v-jun mice lacked the acute hyperplastic response seen in H-2K-v-jun mice.
- Myogenic components were present in H-2K-v-jun tumors but absent in MT-v-jun tumors, indicating different cellular phenotypes and heterogeneity in mesenchymal granulation tissue.
Conclusions:
- The transcriptional regulatory elements driving v-jun expression dictate the specific cell types targeted for oncogenesis.
- Wounding initiates tumorigenesis, but the promoter determines the nature of the resulting wound-induced neoplasms.
- Mesenchymal granulation tissue is heterogeneous, with wound-derived cells possessing different differentiation potentials.