Different Mutant/Wild-Type p53 Combinations Cause a Spectrum of Increased Invasive Potential in Nonmalignant Immortalized Human Mammary Epithelial Cells

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-associat...

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Bibliographic Details
Published in:Neoplasia (New York, N.Y.) N.Y.), 2008-05, Vol.10 (5), p.450-461
Main Authors: Junk, Damian J., Vrba, Lukas, Watts, George S., Oshiro, Marc M., Martinez, Jesse D., Futscher, Bernard W.
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Blotting, Western
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic
Cells, Cultured
Chromatin Immunoprecipitation
Disease Progression
DNA - genetics
DNA - metabolism
Flow Cytometry
Genes, Dominant
Humans
Immunoprecipitation
Mutation - genetics
Neoplasm Invasiveness
Oligonucleotide Array Sequence Analysis
Phenotype
Promoter Regions, Genetic
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
Subcellular Fractions
Telomerase - metabolism
Tumor Stem Cell Assay
Tumor Suppressor Protein p53 - physiology
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Summary: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.
ISSN:1476-5586
1522-8002
1476-5586
1522-8002
DOI:10.1593/neo.08120