Insights into cancer from transgenic mouse models

The generation of mice designed to overexpress activated forms of oncogenes or carrying targeted mutations in tumour suppressor genes, has allowed sci entists to causally link the function of these genes with specific tumour p rocesses, such as proliferation, apoptosis, angiogenesis or metastasis. In addition, these mice have been interbred to assess the extent of cooperativ ity between different genetic lesions in disease progression, leading to a greater understanding of the multi-stage nature of tumourigenesis. The effe ct of genetic mutations is often influenced by the genetic background of th e mouse and by analysing strain-dependent phenotypes, modifier loci have be en identified, Although genetic mutations in mouse and humans do not always lead to the same tumour spectrum, the underlying molecular mechanisms are frequently relevant to both species, Furthermore, new technical approaches creating conditional mouse mutants which develop tumours in a tissue-specif ic manner, will allow the effect of mutation of certain genes to be studied in specific tissues, free from the fatal effects of the mutation in other clinically less relevant tissues, Several exising mouse strains have alread y been used to develop and test new therapies and conditional mutagenesis w ill undoubtedly increase the potential use of transgenic mice in understand ing and treating cancer. Copyright (C) 1999 John Wiley & Sons, Ltd.