Different Mutant/Wild-Type p53 Combinations Cause a Spectrum of Increased Invasive Potential in Nonmalignant Immortalized Human Mammary Epithelial Cells
Year: 2008
Type: article
Abstract: Aberrations of p53 occur in most, if not all, human cancers. In breast cancer, p53 mutation is the most common genetic defect related to a single gene. Immortalized human mammary epithelial cells resemble the earliest forms of aberrant breast tissue growth but do not express many malignancy-associated phenotypes. We created a model of human mammary epithelial tumorigenesis by infecting hTERT-HME1 immortalized human mammary epithelial cells expressing wild-type p53 with four different mutant p53 constructs to determine the role of p53 mutation on the evolution of tumor phenotypes. We demonstrate that different mutant/wild-type p53 heterozygous models generate loss of function, dominant negative activity, and a spectrum of gain of function activities that induce varying degrees of invasive potential. We suggest that this model can be used to elucidate changes that occur in early stages of human mammary epithelial tumorigenesis. These changes may constitute novel biomarkers or reveal novel treatment modalities that could inhibit progression from primary to metastatic breast disease.
Source: Neoplasia
DOI: 10.1593/neo.08120
Institution: University of Arizona
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,530
Funders: National Science Foundation, University of Arizona Cancer Center, Frances McClelland Institute for Children, Youth, and Families, University of Arizona, National Institutes of Health, National Cancer Institute, National Institute of Environmental Health Sciences, Division of Graduate Education
Awards: GENOMIC METHYLATION--A MECHANISM TO ALTER PHENOTYPES, G2159449340, IGERT: Evolutionary, Computational, and Molecular Approaches to Genome Structure and Function, Integrative Cancer Scholars Training Grant, G3551038514, G3901774922, G4222974128, Genomic Methylation: A Mechanism to Alter Tumor Phenotype, G8379774747, G9000010341, G9000142759, Southwest Environmental Health Sciences Center, University of Arizona Cancer Center - Cancer Center Support Grant
OpenAlex ID: W1898075343