Abstract

The histopathology and the epidemiology of human cancers, as well as studies of animal models of tumorigenesis, have led to a widely accepted notion that multiple genetic and epigenetic changes have to accumulate for progression to malignancy. Formation of new blood vessels (tumor angiogenesis) has been recognized, in addition to proliferative capabilities and to the ability to down-modulate cell death (apoptosis), as essential for the progressive growth and expansion of solid tumors beyond microscopic sizes of about 1-2 mm in diameter. Mice overexpressing activated forms of oncogenes or carrying targeted mutations in tumor suppressor genes have proven extremely useful for to linking the function of these genes with specific tumor processes; the interbreeding of these mice let us study the extent of cooperativity between different genetic lesions in disease progression, leading to a greater understanding of multi-stage nature of tumorigenesis.