| Autor: |
Kuperwasser, Charlotte, Hurlbut, Gregory D., Kittrell, Frances S., Dickinson, Ellen S., Laucirica, Rudy, Medina, Daniel, Naber, Stephen P., Jerry, D. Joseph |
| Zdroj: |
American Journal of Pathology; December 2000, Vol. 157 Issue: 6 p2151-2159, 9p |
| Abstrakt: |
Breast cancer is the most frequent tumor type among women in the United States and in individuals with Li-Fraumeni syndrome. The p53tumor suppressor gene is altered in a large proportion of both spontaneous breast malignancies and Li-Fraumeni breast cancers. This suggests that loss of p53can accelerate breast tumorigenesis, yet p53-deficient mice rarely develop mammary tumors. To evaluate the effect of p53loss on mammary tumor formation, the p53nullallele was back-crossed onto the BALB/c genetic background. Median survival was 15.4 weeks for BALB/c-p53−/−mice compared to 54 weeks for BALB/c-p53+/−mice. Sarcomas and lymphomas were the most frequent tumor types in BALB/c-p53−/−mice, whereas 55. of the female BALB/c-p53+/−mice developed mammary carcinomas. The mammary tumors were highly aneuploid, frequently lost the remaining wild-type p53allele, but rarely lost BRCA1. Although mammary tumors were rarely detected in BALB/c-p53−/−female mice, when glands from BALB/c-p53−/−mice were transplanted into wild-type BALB/c hosts, 75% developed mammary tumors. The high rate of mammary tumor development in the BALB/c background, but not C57Bl/6 or 129/Sv, suggests a genetic predisposition toward mammary tumorigenesis. Therefore, the BALB/c-p53+/−mice provide a unique model for the study of breast cancer in Li-Fraumeni syndrome. These results demonstrate the critical role that the p53tumor suppressor gene plays in preventing tumorigenesis in the mammary gland. |
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