A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development.

TitleA mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development.
Publication TypeJournal Article
Year of Publication2000
AuthorsJerry DJ, Kittrell FS, Kuperwasser C, Laucirica R, Dickinson ES, Bonilla PJ, Butel JS, Medina D
JournalOncogene
Volume19
Issue8
Pagination1052-8
Date Published2000 Feb 21
ISSN0950-9232
Keywords9,10-Dimethyl-1,2-benzanthracene, Adenocarcinoma, Aneuploidy, Animals, Carcinogens, Disease Models, Animal, Epithelial Cells, Female, Genes, Tumor Suppressor, Incidence, Mammary Neoplasms, Experimental, Mice, Mice, Inbred BALB C, Neoplasm Transplantation, Pituitary Gland, Pregnancy, Tumor Suppressor Protein p53
Abstract

Although alterations in the p53 tumor suppressor gene are detected frequently in human breast cancers, mammary tumors are observed infrequently in p53(null) mice. This has led to the suggestion that absence of p53 alone is not sufficient for induction of mammary tumors. However, early death of p53(null) mice from thymic lymphomas may obscure tumor phenotypes that would develop later. Therefore, p53(null) mammary epithelium was transplanted into cleared mammary fat pads of wild type p53 BALB/c hosts to allow long-term analysis of mammary tumor phenotypes. Five treatments were compared for their effects on tumor incidence in hosts bearing transplants of p53(null) and p53wt mammary epithelium. The treatment groups were: (1) untreated; (2) continuous hormone stimulation with pituitary isografts; (3) multiple pregnancies; (4) DMBA alone; and (5) DMBA+pituitary isografts. The tumor incidences in p53(null) vs p53wt mammary transplants for each treatment group were 62% vs 0%, 100% vs 0%, 68% vs 0%, 60% vs 4% and 91% vs 14%, respectively. The mammary tumors that developed in the p53(null) mammary epithelium were all adenocarcinomas and were frequently aneuploid. These data demonstrate that the absence of p53 is sufficient to cause development of mammary tumors and that hormonal stimulation enhances the tumorigenicity of p53(null) mammary epithelium to a greater extent than DMBA exposure alone. This model provides an in situ approach to examine the molecular basis for the role of p53 in the regulation of mammary tumorigenesis.

DOI10.1038/sj.onc.1203270
Alternate JournalOncogene
PubMed ID10713689