@article{ad1fe13b88c14ac38cf25b571b72b2cc,
title = "Different mutant/wild-type p53 combinations cause a spectrum of increased invasive potential in nonmalignant immortalized human mammary epithelial cells",
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.",
author = "Junk, {Damian J.} and Lukas Vrba and Watts, {George S.} and Oshiro, {Marc M.} and Martinez, {Jesse D.} and Futscher, {Bernard W.}",
note = "Funding Information: Abbreviations: APAF1, apoptotic peptidase activating factor 1; CDH11, cadherin 11; ChIP, chromatin immunoprecipitation; CSPG2, versican; E2F5, E2F transcription factor 5; FAS, TNF receptor superfamily member 6; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GFP, green fluorescent protein; HME1, hTERT-immortalized human mammary epithelial cells; HMEC, human mammary epithelial cells; MASPIN, mammary serine protease inhibitor; MDM2, mouse double minute; p21, cyclin-dependent kinase inhibitor 1A; PIG11, p53-induced gene 11; PIG12, p53-induced gene 12; PLK3, Polo-like kinase 3; POLH, polymerase (DNA-directed) eta; STAU-2, staufen RNA binding protein homolog 2; TFPI2, tissue factor pathway inhibitor 2; TP53I3, p53-inducible protein 3; TP53INP1, p53-inducible nuclear protein 1; TP53TG1, p53 target gene 1; WIG1, wild-type p53-induced gene 1 Address all correspondence to: Dr. Bernard W. Futscher, Arizona Cancer Center, 1515 N. Campbell Ave., Tucson, AZ 85724-5024. E-mail: bfutscher@azcc.arizona.edu 1We thank Bert Vogelstein for the control and p53 adenoviruses. We thank Douglas W. Cromey, M.S. of the Department of Cell Biology & Anatomy and the Southwest Environmental Health Sciences Center/National Institute of Environmental Health Sciences (NIEHS) grant ES06694 for microscopy. We thank Jos{\'e} Mu{\~n}oz-Rodr{\'i}guez for generating microarray data at the University of Arizona Genomics Shared Service supported by NIEHS grant ES06694, National Institutes of Health (NIH) grant CA23074, and the Bio-5 Institute. D.J. J. was supported in part by a Cancer Biology Training grant CA09213 and an Integrative Graduate Education and Research Traineeship grant NSF DGE 0114420. B.W. F. was supported by NIH grant CA65662. The Arizona Cancer Center also supported this work. Received 7 January 2008; Revised 11 February 2008; Accepted 15 February 2008 Copyright {\textcopyright} 2008 Neoplasia Press, Inc. All rights reserved 1522-8002/08/$25.00 DOI 10.1593/neo.08120",
year = "2008",
month = may,
doi = "10.1593/neo.08120",
language = "English (US)",
volume = "10",
pages = "450--461",
journal = "Neoplasia",
issn = "1522-8002",
publisher = "Elsevier Inc.",
number = "5",
}