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Extreme Expressions of DNA Repair Proteins APE1 and MTH1, in Human Breast Cancer as Measured by Liquid Chromatography and Isotope Dilution Tandem Mass Spectrometry

Published

Author(s)

Erdem Coskun, Pawel Jaruga, Leona D. Scanlan, Alessandro Tona, Mark S. Lowenthal, Prasad T. Reddy, M Miral Dizdar, Ann-Sofie Jemth, Olga Loseva, Thomas Helleday

Abstract

Accurate measurement of DNA repair proteins in cancer tissues is becoming more important due to the individual and origin based expression differences in cancer patients as well as the novel approach of using the repair enzyme inhibitors in cancer treatment. However, available methods for measuring protein levels such as gel-based systems are indirect and not quantitative. Here, we applied an approach using liquid chromatography-tandem mass spectrometry with isotope dilution to accurately measure protein levels in normal and cancerous human breast tissues. We observed extreme expression of APE1 and MTH1 in malignant tumors when compared to disease-free breast tissues, suggesting that breast cancer cells may require these proteins for survival. The novel approach described herein is potentially applicable to the accurate measurement of DNA repair proteins’ expression levels in cancerous vs. normal tissues in patients. This approach may help use APE1 and MTH1 as reliable biomarkers for the development of novel cancer treatment strategies and inhibitors of these proteins as anticancer drugs leading to personalized therapies.
Volume
54
Issue
38
Conference Dates
March 13-17, 2016
Conference Location
New Orleans, LA
Conference Title
The Society of Toxicology 55th Annual Meeting and ToxExpo

Citation

Coskun, E. , Jaruga, P. , Scanlan, L. , Tona, A. , Lowenthal, M. , Reddy, P. , , M. , Jemth, A. , Loseva, O. and Helleday, T. (2015), Extreme Expressions of DNA Repair Proteins APE1 and MTH1, in Human Breast Cancer as Measured by Liquid Chromatography and Isotope Dilution Tandem Mass Spectrometry, The Society of Toxicology 55th Annual Meeting and ToxExpo, New Orleans, LA, [online], https://doi.org/10.1021/acs.biochem.5b00928 (Accessed April 18, 2024)
Created September 15, 2015, Updated January 27, 2020