We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Myc/p53 interactions in transgenic mouse mammary development, tumorigenesis and chromosomal instability.
- Authors
McCormack, Stephen J; Weaver, Zoë; Deming, Sandy; Natarajan, Geraldine; Torri, Jeff; Johnson, Michael D; Liyanage, Marek; Ried, Thomas; Dickson, Robert B
- Abstract
We have examined defects in mammary development and tumorigenesis in a transgenic model expressing the c-myc gene under the MMTV–LTR promoter. The stochastic tumors which arise from hyperplastic ductal and lobular lesions in this model are characterized by high rates both of apoptosis and of chromosomal instability. Since the p53 gene product is thought to be central in the maintenance of genomic integrity, in part due to its ability to induce apoptosis in cells harboring DNA damage, we examined its expression and possible mutation. Initially, we observed that unmutated p53 is strongly expressed in premalignant mammary glands and in mammary tumors derived from the MMTV-c-myc strain. We then mated the MMTV-myc strain to a p53-deficient strain as a means of examining the effect of this lesion on mammary development and tumorigenesis in the context of c-myc overexpression. A lack of both p53 alleles in the presence of c-myc overexpression resulted in a dramatic hyerplastic alteration in mammary gland development. Specifically, in female bitransgenic MMTV-c-myc/p53 null mice (MMTV-myc/p53-/-), lobular hyperplasias were observed at almost every ductal end bud as early as 32 days of age. In contrast, only mild ductal and lobular hyperplasias were seen in MMTV-myc mice that contained both p53 alleles (MMTV-myc/p53+/+); an intermediate phenotype occurred in mice with a single intact (MMTV-myc/p53+/-) p53 allele. Mammary carcinomas arose with a high frequency in MMTV-myc/p53+/- mice; the tumors were comparable in frequency, histology and apoptotic index to the tumors in MMTV-myc/p53+/+ mice. Also, as previously observed (), lymphomas arose with extremely short latency in MMTV-myc/ p53-/- mice, precluding study of the fate of their hyperplastic mammary lesions in situ. The frequency of p53 mutations in MMTV-myc/p53+/+ and MMTV-myc/p53+/- mammary tumors and in cell lines derived...
- Subjects
CARCINOGENESIS; MAMMARY glands; ONCOGENES; TRANSGENIC mice
- Publication
Oncogene, 1998, Vol 16, Issue 21, p2755
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1201804