Genetically Engineered Mice Harboring RAS Mutations as Models of Human Cancer: in Medias RAS

摘要: The molecular and histopathological consequences of expressing a mutated ras gene have been the focus intense studies for past 30 years. Initially, introducing H-ras mutations as transgenes under control heterologous promoter was shown to cause neoplastic changes where expressed, proving in-vivo relevance cancer. Lesions usually developed after long latent period, additional mutation tumor suppressor genes (such p53) resulted in more aggressive phenotype. In an attempt better mimic genetic lesions found human cancer, recent used Cre-Lox recombination system tissue-specific directed endogenous K-ras allele. When expressed lungs, mice develop that include hyperplasias, adenomas, invasive carcinomas, occasionally metastatic lesions. pancreas, early pancreatic intraepithelial (PanIN) are induced, with progression histological atypia appears indistinguishable from disease. Moreover, when crossed conditional Ink4a/ARF background (as is frequently adenocarcinoma), animals succumb both local distant disease within 12 weeks. Similarly, K-rasis hematopoietic cells, all die myeloproliferative disorder. By faithfully recapitulating pathophysiology cognate malignancy, these models provide means dissect relevant pathways leading cancer susceptibility, formation progression; design test prevention, detection, treatment strategies cancers driven by