Acquired resistance of leukemic cells to AraC is associated with the upregulation of aldehyde dehydrogenase 1 family member A2.
Acquired resistance of leukemic cells to AraC is associated with the upregulation of aldehyde dehydrogenase 1 family member A2.
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获得的白血病细胞对ARAC的耐药性与醛脱氢酶1家族成员A2的上调有关。
DOI：
10.1016/j.exphem.2013.03.004
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发表时间：
2013-07
影响因子：
2.6
通讯作者：
Saito, Kuniaki
中科院分区：
文献类型：
--
作者：
Kawasoe, Misaki;Yamamoto, Yasuko;Okawa, Katsuya;Funato, Tadao;Takeda, Mayu;Hara, Takeshi;Tsurumi, Hisashi;Moriwaki, Hisataka;Arioka, Yuko;Takemura, Masao;Matsunami, Hidetoshi;Markey, Sanford P.;Saito, Kuniaki
阐明白血病的耐药机制对于开发治疗白血病的临床疗法具有重要意义。为探讨K562细胞耐药机制，采用双向荧光差异凝胶电泳技术比较1-β-D-阿拉伯呋喃糖基胞嘧啶（AraC）敏感K562（K562 S）细胞和AraC耐药K562（K562 AC）细胞蛋白质表达谱。在蛋白质表达谱的比较中，发现2073个蛋白质点发生了改变，其中15个蛋白质发生了显著改变。这些蛋白质通过质谱鉴定。差异表达最多的蛋白质是醛脱氢酶1家族成员A2（ALDH 1A 2）和波形蛋白。这两种蛋白质进行了验证，使用逆转录聚合酶链反应和蛋白质印迹分析。ALDH 1A 2蛋白在AraC抗性中是有效的。ALDH 1A 2敲低诱导K562 AC细胞对AraC的敏感性，过表达ALDH 1A 2的K562 S细胞获得AraC抗性。此外，研究结果还表明，ALDH 1A 2的表达增加后，在临床病例中出现AraC耐药。这些结果将有助于了解AraC抗性机制。
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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影响因子：
5.1
作者：
Moreb, Jan S.;Ucar, Deniz;Han, Shuhong;Amory, John K.;Goldstein, Alex S.;Ostmark, Blanca;Chang, Lung-Ji
通讯作者：
Chang, Lung-Ji
影响因子：
2.1
作者：
Abraham, Ajay;Varatharajan, Savitha;Balasubramanian, Poonkuzhali
通讯作者：
Balasubramanian, Poonkuzhali
影响因子：
12.8
作者：
Cunningham, Isabel
通讯作者：
Cunningham, Isabel
影响因子：
7
作者：
Zhou, G;Li, HM;Zhao, YM
通讯作者：
Zhao, YM
DOI：
10.1016/j.bbrc.2009.10.094
发表时间：
2009-12-18
影响因子：
3.1
作者：
Jin, Guilan;Matsushita, Hiromichi;Miyachi, Hayato
通讯作者：
Miyachi, Hayato