Summary
Mice bearing the MMTV/c-my transgene predominantly develop mammary
carcinomas. No increased incidence of mammary tumors was observed when the MMTV/c-my
transgene was introduced into a p53 -/- background. This suggests that the the context of
the mammary gland myc and p53 do not collaborate. Mice bearing both the MMTV/c-myc
transgene and a single p53- allele develop very aggressive T-cell lymphomas with a shorter
latency than mice carrying either the p53- allele or the c-myc transgene alone. Cell
context appears to infulence the ability of c-myc amd p53- to cooperate to induce
oncogenesis.
Citation
Elson, A., Deng, X., Campos-Torres, J., Donehower, L.A. and Leder, P.
(1995) The MMTV/c-myc transgene and p53 null alleles collaborate to induce T-cell
lymphomas, but not mammary carcinomas in transgenic mice. Oncogene 11, 181-190.
Conclusions
Oncogene collaboration is cell context specific. The formation of mammary
tumors in MMTV/c-my transgenic mice was not accelerated in a p53 -/- background, which
suggests that in this experimental system p53 does not collaborate with myc. Similarly no
collaboration was seen in the salivary gland. However, p53 does collaborate with myc in
T-cells, and T-cell tumors were accelerated in a p53 -/- background.
The role of p53 in mammary develoment and tumorigenesis is currently not clear. Development of mammary tissue during pregnancy and lactation, apoptosis of alveolar cells during involution, and DMBA induced tumorigenesis do not require functional p53.
mouse strain
The MMTV/c-myc transgene was introduced into a FVB/N background. The p53
mutation was bred from its original background into the FVB/N strain of mice for 5
generations.
key words
MMTV-LTR, transgenic, p53, lymphomas, synergism, mammary gland, oncogenesis
Entered by Lothar Hennighausen on November 10, 1995(e-mail mammary@nih.gov)