Cancer genes: From mouse to man

Abstract

Abstract The number of identified genes involved in the carcinogenic process is constantly increasing. Most of these genes have fundamental roles in cell growth and differentiation, but by different mechanisms they may be converted into cancer promoting genes (proto oncogenes into activated oncogenes and tumour suppressor genes (TSG) into inactivated TSGs. Recently, genes involved in the maintenance and repair of DNA have been found to be involved in cancer development as well. These three groups of genes seems to be highly conserved during evolution, and one of the most studied have been the tumour suppressor gene: TP53. The mouse has historically been used as the mammal of choice for genetic analyses and has served as an important model in cancer research. Gene transfer using the NHI 3T3 mouse cells have identified a number of oncogenes. The construction of transgenic mice has provided insights into the effect of individual oncogenes and TSGs on normal development, cellular proliferation, differentiation, and viability, as well as on oncogene and TSG cooperativity. With the intense mapping of the mouse genome together with the wide range of naturally occurring, chemically induced and transgene induced tumours now available, the mouse is ideal for genetic studies of tumourigenesis in vivo. With the availability of a dense genetic mouse map, loss of heterozygosity (LOH) studies in mouse tumours will be a very powerful approach in identification of new TSGs.