Synergy between a human c-myc transgene and p53 null genotype in murine thymic lymphomas: contrasting effects of homozygous and heterozygous p53 loss

摘要: Activation of the c-myc oncogene and functional loss p53 tumour suppressor gene are among most frequently recorded genetic lesions in neoplasia but their combined effect has not previously been investigated. By breeding together mice transgenic for human (CD2-myc) carrying an inactive allele (p53-/-) we found that these act synergistically vivo. Offspring CD2-myc transgene homozygous null mutation (p53-/-/CD2-myc) were viable developed thymic lymphomas with dramatically increased frequency reduced latency compared to both parental groups. The phenotype was similar (predominantly CD3+, CD4+8+) clonal complexity metastasis significantly greater p53-/-/CD2-myc mice. In contrast, no significant increase incidence seen p53+/-/CD2-myc vs p53+/+/CD2-myc over a 6 month observation period. However, wild type proportion cells suggests can occur as late progression step rather than initiating tumours. We suggest function may collaborate at more one stage lymphoma development.