| AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Am J Transl Res 1(3):249-258;2009
Original Article
Nuclear EGFR is required for Cisplatin Resistance and DNA Repair
Sheng-Chieh Hsu, Stephanie A. Miller, Yan Wang, Mien-Chie Hung
Department of Molecular and Cellular Oncology, The University of M. D. Anderson Cancer Center, Houston, TX
77030, USA
Received February, 2009; accepted February, 2009; available online February, 2009
Abstract: The epidermal growth factor receptor (EGFR) has been shown to be able to translocate to the nucleus
where it is involved in many cellular process including transcriptional regulation and DNA repair. Recently, it has
been shown that the DNA damage-inducing agents ionizing radiation (IR) and cisplatin are able to induce EGFR
nuclear localization, and this nuclear localization is correlated with increased DNA-PK activity, which plays an
essential role in DNA double stranded repair. Here we sought to determine if there is a causal relationship
between nuclear EGFR and DNA repair activity. We found that mutation in the nuclear localization signal (NLS) of
EGFR (mNLS) rendered it unable to translocate to the nucleus and released EGFR induced resistance to
cisplatin. Re-introduction of an NLS in the C-terminal allowed EGFR to re-enter the nucleus and the cells
regained resistance to cisplatin. In addition, we show that the re-expression of a functional nuclear localization
sequence (mNLS-R) is not only able to restore its resistance to cisplatin, but also reduced the DNA damage
caused by cisplatin, and restored DNA repair activity. Thus, we demonstrate here that nuclear EGFR is required
for DNA repair and resistance to cisplatin treatment.(AJTR902002).
Key Words: Epidermal growth factor receptor (EGFR), cisplatin resistance, DNA repair
Full Text PDF
Address all correspondence to:
Mien-Chie Hung, PhD
Department of Molecular and Cellular Oncology
The University of M. D. Anderson Cancer Center
Houston, Texas 77030
USA.
E-mail: mhung@mdanderson.org
Original Article
Nuclear EGFR is required for Cisplatin Resistance and DNA Repair
Sheng-Chieh Hsu, Stephanie A. Miller, Yan Wang, Mien-Chie Hung
Department of Molecular and Cellular Oncology, The University of M. D. Anderson Cancer Center, Houston, TX
77030, USA
Received February, 2009; accepted February, 2009; available online February, 2009
Abstract: The epidermal growth factor receptor (EGFR) has been shown to be able to translocate to the nucleus
where it is involved in many cellular process including transcriptional regulation and DNA repair. Recently, it has
been shown that the DNA damage-inducing agents ionizing radiation (IR) and cisplatin are able to induce EGFR
nuclear localization, and this nuclear localization is correlated with increased DNA-PK activity, which plays an
essential role in DNA double stranded repair. Here we sought to determine if there is a causal relationship
between nuclear EGFR and DNA repair activity. We found that mutation in the nuclear localization signal (NLS) of
EGFR (mNLS) rendered it unable to translocate to the nucleus and released EGFR induced resistance to
cisplatin. Re-introduction of an NLS in the C-terminal allowed EGFR to re-enter the nucleus and the cells
regained resistance to cisplatin. In addition, we show that the re-expression of a functional nuclear localization
sequence (mNLS-R) is not only able to restore its resistance to cisplatin, but also reduced the DNA damage
caused by cisplatin, and restored DNA repair activity. Thus, we demonstrate here that nuclear EGFR is required
for DNA repair and resistance to cisplatin treatment.(AJTR902002).
Key Words: Epidermal growth factor receptor (EGFR), cisplatin resistance, DNA repair
Full Text PDF
Address all correspondence to:
Mien-Chie Hung, PhD
Department of Molecular and Cellular Oncology
The University of M. D. Anderson Cancer Center
Houston, Texas 77030
USA.
E-mail: mhung@mdanderson.org
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