| First Author | Machida Y | Year | 2019 |
| Journal | J Toxicol Pathol | Volume | 32 |
| Issue | 3 | Pages | 197-203 |
| PubMed ID | 31404346 | Mgi Jnum | J:303442 |
| Mgi Id | MGI:6512199 | Doi | 10.1293/tox.2018-0057 |
| Citation | Machida Y, et al. (2019) Increased susceptibility to mammary carcinogenesis and an opposite trend in endometrium in Trp53 heterozygous knockout female mice by backcrossing the BALB/c strain onto the background C3H strain. J Toxicol Pathol 32(3):197-203 |
| abstractText | Patients with dominantly inherited Li-Fraumeni syndrome have a loss-of-function mutation in TP53 and develop diverse mesenchymal and epithelial neoplasms at multiple sites. Trp53 (+/-) female mice with the BALB/c background provide unique characteristics for the study of breast cancer in Li-Fraumeni syndrome; however, we previously found that female C3H-Trp53(+/) (-) mice did not spontaneously develop mammary tumors. Therefore, we obtained F1 and N2-N4 female mice by backcrossing the BALB/c strain and examined the incidence of mammary and other tumors in lifetime studies. Malignant lymphomas, osteosarcomas, and uterine adenocarcinomas spontaneously developed in approximately 20% or more of Trp53(+/) (-) mice with the C3H background. In contrast, the incidence of uterine adenocarcinomas showed a tendency to decrease, while that of mammary adenocarcinomas gradually increased in mice with the BALB/c strain backcross. Wild-type BALB/c female mice are predisposed to a wide spectrum of neoplasms, including mammary tumors, partly due to genetic factors, whereas uterine tumors are uncommon not only in BALB/c mice but also C3H mice. Thus, genetic factors appear to contribute to a strain-specific predisposition to malignant neoplasms in Trp53(+/-) mice, and further studies are needed to clarify the detailed mechanisms. |
