A mouse model system to genetically dissect the molecular mechanisms regulating tumorigenesis.
The vast majority of human tumors are of epithelial origin and result from the accumulation of mutations that alter the function of pathways that control critical cellular processes, including proliferation, checkpoint regulation, and apoptosis. Authentically replicating these events in animal models is critical to understanding the biology of cancer and for testing the feasibility of novel therapies. We developed a mouse model that recapitulates the steps of epithelial tumor progression of multiple tissue types (kidney, breast, ovarian surface, and prostate epithelia), which takes advantage of the power of mouse genetics, and that allows for biochemical analysis, genetic selection, and screening. Moreover, this model enables functional interrogation of far more complex tumor genotypes, both of the tumor cells themselves, and of the cells in the tumor microenvironment. This is a crucial advantage, as human tumors result from multiple compound mutations, most of which are difficult to achieve through standard mutant mouse technology. We have applied this model to establish the role of apoptosis in epithelial solid tumor progression and in treatment response, which has provided novel opportunities for cancer therapies in humans.
Degenhardt
Kurt
K
Center for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854 and Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
White
Eileen
E
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D004843:Epistasis, Genetic; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D052138:Genes, Neoplasm / Q000502:physiology*; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000196:embryology; D008297:Male; D051379:Mice; D023421:Models, Animal; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents