In the 26 April Nature by Tyler Jacks and colleagues at the Department of Biology, Massachusetts Institute of Technology report an improved transgenic mouse model of early onset lung cancer. Johnson et al used a modified gene targeting strategy to generate a mouse strain in which oncogenic alleles of K-ras are activated by spontaneous recombination events (Nature 2001, 410:1111-1116). Because such events occur infrequently — 10-3 to 10-7 per cell generation — the K-ras oncogene was activated at random in some cells. This randomness mimics the sporadic occurrence of K-ras mutations in many human cancers.
The mice showed a high incidence of lung tumours, beginning with the appearance of small pleural nodules at 1 week of age. Histopathology revealed that the tumours evolved through a series of morphological stages, from mild hyperplasia/dysplasia to overt carcinoma, reminiscent of non-small cell lung cancer in humans. Johnson et al conclude that their model ...