Biological and genetic properties of the p53 null preneoplastic mammary epithelium
- 10 April 2002
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 16 (8), 881-883
- https://doi.org/10.1096/fj.01-0885fje
Abstract
The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.Keywords
Funding Information
- National Cancer Institute (U01-CA84243, R01CA84320, R01-CA43322, R01-CA73929)
This publication has 26 references indexed in Scilit:
- Development of Spontaneous Mammary Tumors in BALB/c p53 Heterozygous MiceThe American Journal of Pathology, 2000
- Progesterone facilitates chromosome instability (aneuploidy) in p53 nullThe FASEB Journal, 2000
- A transgenic mouse model for the ductal carcinoma in situ (DCIS) of the mammary glandOncogene, 2000
- A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor developmentOncogene, 2000
- The C3(1)/SV40 T-antigen transgenic mouse model of mammary cancer: ductal epithelial cell targeting with multistage progression to carcinomaOncogene, 2000
- The Preneoplastic Phenotype in Murine Mammary TumorigenesisJournal of Mammary Gland Biology and Neoplasia, 2000
- Genetically engineered mouse models of mammary intraepithelial neoplasia.Journal of Mammary Gland Biology and Neoplasia, 2000
- Mouse Models for Mammary CancerPublished by Springer Science and Business Media LLC ,2000
- The mammary gland: A unique organ for the study of development and tumorigenesisJournal of Mammary Gland Biology and Neoplasia, 1996
- Mammary Tumorigenesis in Chemical Carcinogen-Treated Mice. IV. Induction of Mammary Ductal Hyperplasias2JNCI Journal of the National Cancer Institute, 1976