TY - JOUR
T1 - Acquired resistance of leukemic cells to AraC is associated with the upregulation of aldehyde dehydrogenase 1 family member A2
AU - Kawasoe, Misaki
AU - Yamamoto, Yasuko
AU - Okawa, Katsuya
AU - Funato, Tadao
AU - Takeda, Mayu
AU - Hara, Takeshi
AU - Tsurumi, Hisashi
AU - Moriwaki, Hisataka
AU - Arioka, Yuko
AU - Takemura, Masao
AU - Matsunami, Hidetoshi
AU - Markey, Sanford P.
AU - Saito, Kuniaki
N1 - Funding Information:
The authors thank Dr. Y. Ohta for scientific discussing and proofreading the manuscript. This study was supported in part by a Grant-in-Aid from the Ministry of Education, Science and Culture of Japan ( 23390149 to K.S. and 23790621 Y.Y.) and a grant from the Smoking Research Foundation .
PY - 2013/7
Y1 - 2013/7
N2 - The elucidation of drug resistance mechanisms is important in the development of clinical therapies for the treatment of leukemia. To study the drug resistance mechanisms, protein expression profiles of 1-β-D-arabinofuranosylcytosine (AraC)-sensitive K562 (K562S) cells and AraC-resistant K562 (K562AC) cells were compared using two-dimensional fluorescence difference gel electrophoresis. In a comparison of protein expression profiles, 2073 protein spots were found to be altered, and 15 proteins of them were remarkably altered. These proteins were identified by mass spectrometry. The most differently expressed proteins were aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and vimentin. Both proteins were verified using reverse transcriptase polymerase chain reaction and Western blot analysis. ALDH1A2 protein was found to be effective in AraC resistance. ALDH1A2 knock-down induced sensitivity to AraC treatment in K562AC cells, and ALDH1A2 overexpressed K562S cells acquired the AraC resistance. Furthermore, the findings also suggest that ALDH1A2 expression is increased after the appearance of AraC resistance in clinical cases. These results will be helpful in understanding the mechanism of AraC resistance.
AB - The elucidation of drug resistance mechanisms is important in the development of clinical therapies for the treatment of leukemia. To study the drug resistance mechanisms, protein expression profiles of 1-β-D-arabinofuranosylcytosine (AraC)-sensitive K562 (K562S) cells and AraC-resistant K562 (K562AC) cells were compared using two-dimensional fluorescence difference gel electrophoresis. In a comparison of protein expression profiles, 2073 protein spots were found to be altered, and 15 proteins of them were remarkably altered. These proteins were identified by mass spectrometry. The most differently expressed proteins were aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and vimentin. Both proteins were verified using reverse transcriptase polymerase chain reaction and Western blot analysis. ALDH1A2 protein was found to be effective in AraC resistance. ALDH1A2 knock-down induced sensitivity to AraC treatment in K562AC cells, and ALDH1A2 overexpressed K562S cells acquired the AraC resistance. Furthermore, the findings also suggest that ALDH1A2 expression is increased after the appearance of AraC resistance in clinical cases. These results will be helpful in understanding the mechanism of AraC resistance.
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U2 - 10.1016/j.exphem.2013.03.004
DO - 10.1016/j.exphem.2013.03.004
M3 - Article
C2 - 23507523
AN - SCOPUS:84879605537
SN - 0301-472X
VL - 41
SP - 597-603.e2
JO - Experimental Hematology
JF - Experimental Hematology
IS - 7
ER -
