Next Article in Journal
Optimization of NaOH Molarity, LUSI Mud/Alkaline Activator, and Na2SiO3/NaOH Ratio to Produce Lightweight Aggregate-Based Geopolymer
Next Article in Special Issue
Periostin Expression and Its Prognostic Value for Colorectal Cancer
Previous Article in Journal
Vasa Vasorum in Atherosclerosis and Clinical Significance
Previous Article in Special Issue
Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2015, 16(5), 11609-11628; doi:10.3390/ijms160511609

Spontaneous γH2AX Foci in Human Solid Tumor-Derived Cell Lines in Relation to p21WAF1 and WIP1 Expression

1
Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada
2
Division of Nephrology, Department of Internal Medicine, University of California, Davis, CA 95616, USA
3
Department of Medicine, Mather VA Medical Center, Sacramento, CA 95655, USA
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 15 April 2015 / Revised: 12 May 2015 / Accepted: 15 May 2015 / Published: 20 May 2015
(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment)
View Full-Text   |   Download PDF [6643 KB, uploaded 20 May 2015]   |  

Abstract

Phosphorylation of H2AX on Ser139 (γH2AX) after exposure to ionizing radiation produces nuclear foci that are detectable by immunofluorescence microscopy. These so-called γH2AX foci have been adopted as quantitative markers for DNA double-strand breaks. High numbers of spontaneous γH2AX foci have also been reported for some human solid tumor-derived cell lines, but the molecular mechanism(s) for this response remains elusive. Here we show that cancer cells (e.g., HCT116; MCF7) that constitutively express detectable levels of p21WAF1 (p21) exhibit low numbers of γH2AX foci (<3/nucleus), whereas p21 knockout cells (HCT116p21−/−) and constitutively low p21-expressing cells (e.g., MDA-MB-231) exhibit high numbers of foci (e.g., >50/nucleus), and that these foci are not associated with apoptosis. The majority (>95%) of cells within HCT116p21−/− and MDA-MB-231 cultures contain high levels of phosphorylated p53, which is localized in the nucleus. We further show an inverse relationship between γH2AX foci and nuclear accumulation of WIP1, an oncogenic phosphatase. Our studies suggest that: (i) p21 deficiency might provide a selective pressure for the emergence of apoptosis-resistant progeny exhibiting genomic instability, manifested as spontaneous γH2AX foci coupled with phosphorylation and nuclear accumulation of p53; and (ii) p21 might contribute to positive regulation of WIP1, resulting in dephosphorylation of γH2AX. View Full-Text
Keywords: p21WAF1; WIP1; γH2AX foci; p53; apoptosis p21WAF1; WIP1; γH2AX foci; p53; apoptosis
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Mirzayans, R.; Andrais, B.; Scott, A.; Wang, Y.W.; Weiss, R.H.; Murray, D. Spontaneous γH2AX Foci in Human Solid Tumor-Derived Cell Lines in Relation to p21WAF1 and WIP1 Expression. Int. J. Mol. Sci. 2015, 16, 11609-11628.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top