Molecular comparison of human and mouse pulmonary adenocarcinomas.
Mice develop lung tumors similar in their histogenesis and molecular features to peripheral adenocarcinomas in humans. The advantage of this model system is that events early in tumorigenesis can be delineated and their biological consequences tested by transgenic and knockout strategies. Both human and murine adenocarcinomas contain Kras mutations; in mice these occur within weeks following carcinogen administration. Decreased expression of similar tumor suppressor genes occur in both species due to mutation, deletion, altered DNA methylation, or unknown mechanisms. These genes include p15, p16, Rb, cyclin D1, p53, Apc, Mcc, and Gjal. Some genes have only been examined in one of these species, such as the deletions in chromosome 3p and the overexpression of bcl 2 in human adenocarcinoma. Not all molecular changes are identical to the two species, however. Quinone oxidoreductase (DT-diaphorase) levels rise in the human tumors but fall in the mouse; the extent of both changes is very dramatic. Similarly, EGF-receptor content often increases in human lung adenocarcinomas but decreases in the mouse tumors. In general, however, the nature of the molecular changes is quite similar.
Malkinson
A M
AM
Department of Pharmaceutical Sciences, School of Pharmacy and Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, USA. Al.Malkinson@UCHSC.edu
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000473:pathology; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D004195:Disease Models, Animal; D018450:Disease Progression; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D017354:Point Mutation; D013045:Species Specificity
D004273:DNA, Neoplasm