title: Biological and genetic properties of the p53 null preneoplastic mammary epithelium.
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.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. dmedina@bcm.tmc.edu
authors.forename: Daniel
authors.initials: D
authors.lastname: Medina
authors.forename: Frances S
authors.initials: FS
authors.lastname: Kittrell
authors.forename: Anne
authors.initials: A
authors.lastname: Shepard
authors.forename: L Clifton
authors.initials: LC
authors.lastname: Stephens
authors.forename: Cheng
authors.initials: C
authors.lastname: Jiang
authors.forename: Junxuan
authors.initials: J
authors.lastname: Lu
authors.forename: D Craig
authors.initials: DC
authors.lastname: Allred
authors.forename: Maureen
authors.initials: M
authors.lastname: McCarthy
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ullrich
mesh_terms: D000782:Aneuploidy; D000818:Animals; D002278:Carcinoma in Situ / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005838:Genotype; D006965:Hyperplasia; D066298:In Vitro Techniques; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology*; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011960:Receptors, Estrogen / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53