Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML).
Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML).
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DOI：
10.1371/journal.pone.0002594
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发表时间：
2008-07-09
期刊：
影响因子：
3.7
通讯作者：
Moon C
中科院分区：
文献类型：
--
作者：
Chae YK;Kang SK;Kim MS;Woo J;Lee J;Chang S;Kim DW;Kim M;Park S;Kim I;Keam B;Rhee J;Koo NH;Park G;Kim SH;Jang SE;Kweon IY;Sidransky D;Moon C
水通道蛋白（AQP）先前已与实体瘤中的表达增加相关。然而，其在血液系统恶性肿瘤包括CML中的表达尚未被描述。我们采用RT-PCR和免疫组化方法检测了慢性粒细胞白血病细胞中AQP 5的表达。虽然正常骨髓活检样品（n = 5）显示没有AQP 5的表达，32%的CML患者样品（n = 41）显示AQP 5的表达。 此外，AQP 5表达水平随着配对样本中甲磺酸伊马替尼耐药的出现而增加（p = 0.047）。 我们发现AQP 5在K562细胞中的过表达导致细胞增殖增加。此外，靶向AQP 5的小干扰RNA（siRNA）降低了K562和LAMA 84 CML细胞的细胞增殖率。此外，通过免疫印迹和流式细胞术，我们发现BCR-ABL 1的磷酸化在AQP 5过表达的CML细胞中增加，而在AQP 5 siRNA处理的CML细胞中减少。有趣的是，caspase 9活性在AQP 5 siRNA处理的细胞中增加。最后，FISH显示没有证据表明AQP 5基因扩增CML骨髓。综上所述，我们首次报道了AQP 5在CML细胞中过表达，并在促进细胞增殖和抑制细胞凋亡中起作用。此外，我们的研究结果可能提供一种新的慢性粒细胞白血病治疗靶向AQP 5的基础。
Aquaporins (AQPs) have previously been associated with increased expression in solid tumors. However, its expression in hematologic malignancies including CML has not been described yet. Here, we report the expression of AQP5 in CML cells by RT-PCR and immunohistochemistry. While normal bone marrow biopsy samples (n = 5) showed no expression of AQP5, 32% of CML patient samples (n = 41) demonstrated AQP5 expression. In addition, AQP5 expression level increased with the emergence of imatinib mesylate resistance in paired samples (p = 0.047). We have found that the overexpression of AQP5 in K562 cells resulted in increased cell proliferation. In addition, small interfering RNA (siRNA) targeting AQP5 reduced the cell proliferation rate in both K562 and LAMA84 CML cells. Moreover, by immunoblotting and flow cytometry, we show that phosphorylation of BCR-ABL1 is increased in AQP5-overexpressing CML cells and decreased in AQP5 siRNA-treated CML cells. Interestingly, caspase9 activity increased in AQP5 siRNA-treated cells. Finally, FISH showed no evidence of AQP5 gene amplification in CML from bone marrow. In summary, we report for the first time that AQP5 is overexpressed in CML cells and plays a role in promoting cell proliferation and inhibiting apoptosis. Furthermore, our findings may provide the basis for a novel CML therapy targeting AQP5.
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DOI：
10.1152/ajpgi.00480.2003
发表时间：
2004-07-01
影响因子：
4.5
作者：
Gresz, V;Kwon, TH;Nielsen, S
通讯作者：
Nielsen, S
影响因子：
6.6
作者：
Kageyama, Y;Sasaki, S;Ikawa, Y
通讯作者：
Ikawa, Y
影响因子：
8
作者：
Moon, C;Soria, JC;Mao, L
通讯作者：
Mao, L
DOI：
10.1073/pnas.95.6.2991
发表时间：
1998-03-17
影响因子：
11.1
作者：
Dobbs, LG;Gonzalez, R;Verkman, AS
通讯作者：
Verkman, AS
影响因子：
8.8
作者：
Saadoun, S;Papadopoulos, MC;Davies, DC;Bell, BA;Krishna, S
通讯作者：
Krishna, S