水通道蛋白在卵巢上皮性癌中的表达及对细胞顺铂敏感性的影响
|
摘要
水通道蛋白(Aquaporins AQPs)是水分子跨越细胞的快速转运通道,广泛分布于机体组织细胞,主要介导细胞内外的水分子运输,对维持细胞内水平衡具有重要作用。研究表明,多种恶性肿瘤存在水通道蛋白的异常表达,水通道蛋白在肿瘤的增殖、浸润转移中具有重要作用。为探讨水通道蛋白在卵巢癌中的表达与功能,本文选择以下两部分进行研究。
第一部分水通道蛋白亚型在卵巢上皮性肿瘤组织中的表达
已发现在卵巢癌组织表达的水通道亚型包括：AQP1、AQP3、AQP5,为明确其他水通道蛋白亚型在卵巢上皮性肿瘤的分布表达,本研究利用免疫组化技术分析AQP2、AQP4、AQP6、AQP7、AQP8、AQP9在卵巢上皮性肿瘤的分布情况,发现AQP6、AQP8、AQP9表达于卵巢上皮性肿瘤细胞,AQP2、AQP7、AQP7表达不明显。Western blot分析表明,其中AQP6在卵巢浆液性癌中表达下降；AQP9在粘液性肿瘤表达增高,AQP8在卵巢肿瘤中表达无显著差异,提示水通道蛋白在卵巢上皮性肿瘤中表达存在不同的分布与功能。
第二部分：水通道蛋白对卵巢癌细胞顺铂敏感性的影响
水通道蛋白作为水的跨膜膜转运体其与他转运体密切相关,细胞水通透性及细胞水代谢可能影响肿瘤细胞对化疗药物的敏感性。本文利用RT-PCR检测DDP作用下卵巢癌细胞SKOV3的水通道蛋白亚型表达变化,MTT分析水通道阻滞和细胞外渗透压改变对顺铂(DDP)细胞增殖抑制作用的影响,通过体外实验研究水通道蛋白对卵巢癌细胞DDP敏感性中的作用。结果表明,水通道蛋白阻滞和细胞外高渗增加顺铂对癌细胞的增殖抑制作用；顺铂作用后卵巢癌细胞水通道白亚型表现为不同的反应性改变,随药物作用时间的延长,AQP1表达下调与AQP3、AQP8表达增加,提示细胞水通透性影响顺铂的药物敏感性,卵巢癌细胞水通道蛋白与化疗药物敏感性及耐药密切相关。
以上研究表明,不同的水通道蛋白亚型卵巢肿瘤的发生、发展过程中可能具有不同的作用,水通道蛋白相关的细胞水代谢与卵巢癌的化疗敏感性密切相关。对水通道蛋白表达与卵巢癌关系的研究,将为卵巢癌发病机制研究提供新的方向,对化疗药物敏感性的研究将为卵巢癌化学治疗及肿瘤耐药治疗提供新的切入点。
Aquaporins(AQPs) are specialized channels to quickly transport water across cell plasma membranes, which are distributed in mammal tissue extensively. AQPs is essential for cell to maintain water balance. Studies have shown that AQPs are strongly expressed in neoplasm of different origins, and they may play important roles in cell proliferation and migration of agressisve tumor. The present study aims at investigating the role of aquaporins in the epithelia ovarian carcinoma. The study was divided into two parts:1. expression of AQPs in epithelia ovarian tumor; 2. effect of AQPs on chemosensitivity to cisplatin in ovarian cancer.
Part one Expression of aquaporins in epithelia ovarian tumor
Previous study showed that some AQPs became upgrated in ovarian carcinoma, including AQP1, AQP3 and AQP5. To discovery the other subtype of aquaporin in epithelia ovarian tumor, immunohistochemical technique and western botting were used to detect the protein expression of AQP2, AQP4, AQP6, AQP7, AQP8 and AQP9. Immunohistochemical study show AQP6, AQP8 and AQP9 were expressed in ovarian tumor, but AQP2, AQP4 and AQP7 were not. The protein expression of AQP6 in serous ovarian cancer significantly decreased than that of benign tumor and normal tissue, and AQP9 expression significantly increased in mucinous tumors. There were no difference of AQP8 expression between malignant and benign tumors. These data indicated that there are different distribution and function of aquaporins in ovarian tumor.
Part two Effects of aquaporins on chemosensitivity to cisplatin in ovarian cancer cells
As a water transporter, aquaporins are closely related to other membrane transporters, and water permeability metabolism in cell may contribute to chemosensitivity of tumor. In this study, effects of cisplatin on aquaporins mRNA expression ovarian cancer cell SKOV3 were measured by RT-PCR. To understand the role of aquaporins on cell proliferation of SKOV3, chemosensitivity to cisplatin was observed in hypertoncity and aquaporin inhibition. MTT analyses showed that aquqporin blocker and hypertonicity increased the sensitivity of SKOV3 to cisplatin. The effects of cisplatin on SKOV3 are different between different subtype of aquaporin, following incubation time increasing, the expression of AQP1 mRNA decreased significantly, but expression of AQP3 and AQP8 increased. This results show that aquaporins may play an important role in chemosensivity of ovarian cancer.
In conclusion, our studies have shown that different subtypes of aquaporins may play different roles in ovarian tumors, and aquaporins are associated with chemotherapy sensitivity of ovarian cancer. The research of aquaporins in ovarian cancer will provide a new direction for the pathogenesis of ovarian cancer and drug sensitivity studies for chemotherapy.
第一部分水通道蛋白亚型在卵巢上皮性肿瘤组织中的表达
已发现在卵巢癌组织表达的水通道亚型包括：AQP1、AQP3、AQP5,为明确其他水通道蛋白亚型在卵巢上皮性肿瘤的分布表达,本研究利用免疫组化技术分析AQP2、AQP4、AQP6、AQP7、AQP8、AQP9在卵巢上皮性肿瘤的分布情况,发现AQP6、AQP8、AQP9表达于卵巢上皮性肿瘤细胞,AQP2、AQP7、AQP7表达不明显。Western blot分析表明,其中AQP6在卵巢浆液性癌中表达下降；AQP9在粘液性肿瘤表达增高,AQP8在卵巢肿瘤中表达无显著差异,提示水通道蛋白在卵巢上皮性肿瘤中表达存在不同的分布与功能。
第二部分：水通道蛋白对卵巢癌细胞顺铂敏感性的影响
水通道蛋白作为水的跨膜膜转运体其与他转运体密切相关,细胞水通透性及细胞水代谢可能影响肿瘤细胞对化疗药物的敏感性。本文利用RT-PCR检测DDP作用下卵巢癌细胞SKOV3的水通道蛋白亚型表达变化,MTT分析水通道阻滞和细胞外渗透压改变对顺铂(DDP)细胞增殖抑制作用的影响,通过体外实验研究水通道蛋白对卵巢癌细胞DDP敏感性中的作用。结果表明,水通道蛋白阻滞和细胞外高渗增加顺铂对癌细胞的增殖抑制作用；顺铂作用后卵巢癌细胞水通道白亚型表现为不同的反应性改变,随药物作用时间的延长,AQP1表达下调与AQP3、AQP8表达增加,提示细胞水通透性影响顺铂的药物敏感性,卵巢癌细胞水通道蛋白与化疗药物敏感性及耐药密切相关。
以上研究表明,不同的水通道蛋白亚型卵巢肿瘤的发生、发展过程中可能具有不同的作用,水通道蛋白相关的细胞水代谢与卵巢癌的化疗敏感性密切相关。对水通道蛋白表达与卵巢癌关系的研究,将为卵巢癌发病机制研究提供新的方向,对化疗药物敏感性的研究将为卵巢癌化学治疗及肿瘤耐药治疗提供新的切入点。
Aquaporins(AQPs) are specialized channels to quickly transport water across cell plasma membranes, which are distributed in mammal tissue extensively. AQPs is essential for cell to maintain water balance. Studies have shown that AQPs are strongly expressed in neoplasm of different origins, and they may play important roles in cell proliferation and migration of agressisve tumor. The present study aims at investigating the role of aquaporins in the epithelia ovarian carcinoma. The study was divided into two parts:1. expression of AQPs in epithelia ovarian tumor; 2. effect of AQPs on chemosensitivity to cisplatin in ovarian cancer.
Part one Expression of aquaporins in epithelia ovarian tumor
Previous study showed that some AQPs became upgrated in ovarian carcinoma, including AQP1, AQP3 and AQP5. To discovery the other subtype of aquaporin in epithelia ovarian tumor, immunohistochemical technique and western botting were used to detect the protein expression of AQP2, AQP4, AQP6, AQP7, AQP8 and AQP9. Immunohistochemical study show AQP6, AQP8 and AQP9 were expressed in ovarian tumor, but AQP2, AQP4 and AQP7 were not. The protein expression of AQP6 in serous ovarian cancer significantly decreased than that of benign tumor and normal tissue, and AQP9 expression significantly increased in mucinous tumors. There were no difference of AQP8 expression between malignant and benign tumors. These data indicated that there are different distribution and function of aquaporins in ovarian tumor.
Part two Effects of aquaporins on chemosensitivity to cisplatin in ovarian cancer cells
As a water transporter, aquaporins are closely related to other membrane transporters, and water permeability metabolism in cell may contribute to chemosensitivity of tumor. In this study, effects of cisplatin on aquaporins mRNA expression ovarian cancer cell SKOV3 were measured by RT-PCR. To understand the role of aquaporins on cell proliferation of SKOV3, chemosensitivity to cisplatin was observed in hypertoncity and aquaporin inhibition. MTT analyses showed that aquqporin blocker and hypertonicity increased the sensitivity of SKOV3 to cisplatin. The effects of cisplatin on SKOV3 are different between different subtype of aquaporin, following incubation time increasing, the expression of AQP1 mRNA decreased significantly, but expression of AQP3 and AQP8 increased. This results show that aquaporins may play an important role in chemosensivity of ovarian cancer.
In conclusion, our studies have shown that different subtypes of aquaporins may play different roles in ovarian tumors, and aquaporins are associated with chemotherapy sensitivity of ovarian cancer. The research of aquaporins in ovarian cancer will provide a new direction for the pathogenesis of ovarian cancer and drug sensitivity studies for chemotherapy.
引文
1. Verkman AS, Mitra AK. Structure and function of aquaporin water channels. Am J Physiol,2000,278:F13-F28.
2. Fulvio Magni, Gecilia Sarto, Davide Ticozzi, et al. Proteomic knowledge of human aquaporins. Proteomics,2006,6:5637-5649。
3. Gonen T, Walz T. The structure of aquaporins. Q Rev Biophys 2006,39:361-396.
4. Ishibashi K, Kuwahara M, Gu Y, et al. (1998) Cloning and functional expression of a new aquaporin (AQP9) abundantly expressed in the peripheral leukocytes per-meable to water and urea, but not to glycerol. Biochem Biophys Res Commun, 1998,244:268-274.
5. M.C Papadopoulos, S.Saadoun, A.S Verkman. Aquaporins and cell migration. Pflugers Arch-Eur J Physiol,2008,456:693-700.
6. Hibuse T, Maeda N, Nagasawa A, et al. Aquaporins and glycerol metabolism. Biochimica Biophysica Acta,2006,1758:1004-1011.
7. Mobasheri A, Airlew R, Hewitt SM, et al. Heterogeneous expression of the aquaporin1(AQP1)water channel in tumors of the prostate, breast, ovary, colon and lung:a study using high density multiple human tumor tissue mocroarrays. Int J Oncol,2005,26:1149-1158.
8. Yang JH, Shi YF, Chen XD et al. The influence of aquaporin-1 and microvessel density on ovarian carcinogenesis and ascites formation Int J Gynecol Cancer 2006;16(Suppl, 1):400-405.
9.杨建华,石一复,程琪等.卵巢上皮性肿瘤患者AQP1蛋白及mRNA的表达及意义.中华妇产科杂志,2005,40(9)：623-626.
10. Yang JH, Shi YF, Chen Q et al. Expression and localization of aquaporin-5 in the epithelial ovarian tumor. Gynecologic Oncology,2006,100 (2):294-299.
11.李留霞,赵艳萍,文建国等.卵巢上皮性癌组织中水通道蛋白3的表达.郑州大学学报(医学版),2008,43(2)：329-332.
12. Agre P, King LS, Yasui M, et al. Aquaporin water channels-from atomic structure to clinical medicine. J Physiol,2002,542:3-16
13. A.S Verkman, Mariko Hara-Chikuma. Aquaporins-new players in cancer biology. J Mol Med,2008,86:523-529
14. Eric Mccoy, Harald Sontheimer. Expression and function of water channels (Aquaporins) in migration malignant astrocytes. Glia,2007 55:1034-1043.
15. Young Kwang Chae, Janghee Woo, Mi-Jung Kim, et al. Expression of aquaporin 5 promotes tumor invasion in human non small cell lung cancer. Plos ONE,2008, 5(2162):1-9.
16. Yasui M, Hazama A, Kwon TH, et al. Rapid gating and anion permeability of an intracellular aquaporin. Nature 1999,402(6758):184-187.
17. Yasui M. pH regulated anion permeability of aquaporin-6. Handb Exp Pharmacol. 2009, (190):299-308.
18. Hazama A, Kozono D, Guggino WB, et al. Ion permea-tion of AQP6 water channel protein. Single channel record-ings after Hg2+ activation. J Biol Chem 2002,277(32):29224-29230.
19. Ikeda M, Beitz E, Kozono D, et al. Charac-terization of aquaporin-6 as a nitrate channel in mammalian cells. Requirement of pore-lining residue threonine 63. J Biol Chem 2002,277(42):39873-39879.
20. Liu K, Kozono D, Kato Y, et al. Conversion of aquaporin 6 from an anion channel to a water-selective channel by a single amino acid substitution. Proc Natl Acad Sci USA,2005,102(6):2192-2197.
21. Yasui M, Kwon TH, Knepper MA, et al. Aquaporin-6:An intracellular vesicle water channel protein in renal epithelia. Proc Natl Acad Sci USA 1999,96(10): 5808-5813.
22. Nagase H, Agren J, Saito A, et al. Molec-ular cloning and character- ization of mouse aquaporin 6. Bio-chem Biophys Res Commun 2007,352(1):12-16.
23. Lopez IA, Ishiyama G, Lee M, et al. Immunohisto-chemical localization of aquaporins in the human inner ear.Cell Tissue Res 2007,328(3):453-460.
24. Matsuki-Fukushima M, Hashimoto S, Shimono M, et al. Presence and localization of aquaporin-6 in rat parotid acinar cells. Cell Tissue Res 2008,332(1):73-80.
25. Umberto L, Giulia G, Mariarosa P, et al. Aquaporin-6 is expression along the rat gastrointestinal tract and upregulated by feeding in the small intestine. BMC Physiology,2009,9:18.
26. Jablonski EM, Mattocks MA, Sokolov E et al. Decreased aquaporin expression leads to increased resistance to apoptosis in hepatocellular carcinoma. Cancer Lett. 2007,250(1):36-46.
27. Matsuzaki T, Tajika Y, Tserentsoodol N, et al. Aquaporins:a water channel family. Anat Sci Int,2002,77(2):85-93.
28. Wang S, Chen J, Katherine T, et al. Expression of aquaporin-8 and its up-regulation by cyclic adenosine monophosphate in human WISH cells. Am J Obstet Gynecol,2003,188:997-1001.
29. Mock N, McConnell NA, Hughes FM. Potential role of aquaporins in the formation and expansion of the ovarian follicular antrum and their regulation by gonadotropins. Recent research developments in endocrinology,2004,4 (1): 169-179.
30. Calamita G, Ferri D, Gena P, et al. The inner mitochondrial membrane has aquaporin-8 water channels and is hishly permeable to water. Journal of Biological Chemistry,2005,280(17):17149-17153.
31. Gonen T, Walz T. The structure of aquaporins. Q Rev Biophys 2006,39:361-396.
32. Tsukaguchi H, Weremowicz S, Morton CC, et al. Functional and molecular characterization of the human neutral solute channel aquaporin-9. Am J Physiol, 1999,277:F685-F696.
33. Ishibashi K, Kuwahara M, Gu Y, et al. Cloning and functional expression of a new aquaporin (AQP9) abundantly expressed in the peripheral leukocytes per-meable to water and urea, but not to glycerol. Biochem Biophys Res Commun,1998,244: 268-274.
34. Tsukaguchi H, Weremowicz S, Morton CC, et al. Functional and molecular characterization of the human neutral solute channel aquaporin-9. Am J Physiol, 1999,277:F685-F696.
35. Tsukaguchi H, Shayakul C, Berger UV, et al. Molecular characterization of a broad selectivity neutral solute channel. J Biol Chem,1998 273:24737-24743.
36. Holm LM, Jahn TP, Moller AL, et al. NH3 and NH4 permeability in aquaporin
-expressing Xenopus oocytes. Pflugers Arch,2005,450:415-428.
37. Ko SB, Uchida S, Naruse S, et al. Cloning and functional expression of rAOP9L a new member of aquaporin family from rat liver. Biochem Mol Biol Int,1999, 47:309-318.
38. Elkjaer M, Vajda Z, Nejsum LN, et al. Immunolocalization of AQP9 in liver, epididymis, testis, spleen, and brain. Biochem Biophys Res Commun,2000,276: 1118-1128
39. Badaut J, Hirt L, Granziera C, et al. Astrocyte-specific expression of aquaporin-9 in mouse brain is increased after transient focal cerebral ischemia. J Cereb Blood Flow Metab,2001,21:477-482.
40. Badaut J, Petit JM, Brunet JF, et al. Distribution of aquaporin 9 in the adult rat brain preferential expression in catecholaminergic neurons and in glia cells. Neuroscience,2004,128:27-38.
41. Oshio K, Binder DK, Yang B, et al. Expression of aquaporin water channels in mouse spinal cord. Neuroscience,2004,127:685-693.
42. Pastor-Soler N, Isnard-Bagnis C, Herak-Kramberger C et al. Expression of aquaporin 9 in the adult rat epididymal epithelium is modulated by androgens. Biology of Reproduction,2002,66:1716-1722.
43.刘絮,张忠芳,赵丹等.不同发育阶段大鼠睾丸水通道蛋白AQP9的表达研究.北华大学学报,2004,5：509-511.
44. Beall MH, van den Wijngaard JP, van Gemert MJ, et al. Regulation of amniotic fluid volume. Placenta,2007,28:824-32.
45. Wang S, Chen J, Huang B, et al. Cloning and cellular expression of aquaporin 9 in ovine fetal membranes. Am J Obstet Gynecol 2005,193:841-8.
46. Damiano A, Zotta E, Goldstein J, et al. Water channel proteins AQP3 and AQP9 are present in syncytiotrophoblast of human term placenta. Placenta,2001, 22:776-81.
47. de Castro Ribeiro M, Hirt L, Bogousslavsky J, et al. Time course of aquaporin expression after transient focal cerebral ischemia in mice. J Neurosci Res,2006, 83:1231-1240.
48. Leung J, Pang A, Yuen WH, et al. Relationship of expression of aqua-glyceroporin 9 with arsenic uptake and sensitivity in leukemia cells. Toxicol In Vitro.2009, 23(2):209-16.
49. Warth A, Mittelbronn M, Hulper P, et al. Expression of the water channel protein aquaporin-9 in malignant brain tumors. Appl Immunohistochem Mol Morphol. 2007,15(2):193-8.
1. A.S Verkman, Mariko Hara-Chikuma. Aquaporins-new players in cancer biology. J Mol Med,2008,86:523-529
2. Saadoun S, Papadopoulous MC et al. Increased aquaporin 1 water channel expression in human brain tumors. Br J Cancer.2002,87(6):621-623.
3. Saadoun S, Papadopoulous MC et al. Aquaporin-4 expression is increased in oedematous human brain tumors. J Neurol Neurosurg Psychiatry.2002, 72(2):262-265
4. Hara-Chikuma M, Verkman AS. Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption. Mol Cell Biol.2008,28(1):326-32.
5. Huang Y, Murakami T, Sano F. Expression of Aquaporin 1 in Primary Renal Tumors:A Prognostic Indicator for Clear-Cell Renal Cell Carcinoma. Eur Urol. 2008 Oct 14.
6. Fischer H, Stenling R, Carlos B, et al. Differential expression of aquaporin 8 in human colonic epithelial cells and colorectal tumors. BMC Physic.2001,1:1
7. Moon C, Soria JC, Jaug SJ, et al. Involvement of aquaporins in colreetal omeinogenesis. Oncogene.2003,22(43):6699-6703.
8. Hoque MO, Soria JC, Woo J, et al. Aquaporin 1 is overexpressed in lung cancer and stimulates NIH-3T3 cell proliferation and anchorage-independent growth. Am J Pathol.2006,168(4):1345-53.
9. Chae YK, Woo J, Kim MJ et al. Expression of aquaporin 5 (AQP5) promotes tumor invasion in human non small cell lung cancer. PLoS ONE.2008, 14;3(5):e2162.
10. Eric Mccoy, Harald Sontheimer. Expression and function of water channels (Aquaporins) in migration malignant astrocytes. Glia 2007 55:1034-1043.
11. Young Kwang Chae, Janghee Woo, Mi-Jung Kim, et al. Expression of aquaporin 5 promotes tumor invasion in human non small cell lung cancer. Plos ONE,2008, 5(2162):1-9.
12. Yang JH, Shi YF, Cheng Q, et al. Expression and localization of aquaporin-5 in the epithelial ovarian tumor. Gynecologic Oncology.2006,100(2):294-299
13. Yang JH, Shi YF, Chen XD, Qi WJ. The influence of aquaporin-1 and microvessel density on ovarian carcinogenesis and ascites formation. Int J Gynecol Cancer. 2006,16(Suppl.):400-405
14.杨建华,郑伟,石一复,陈学军.顺铂对卵巢癌SKOV3细胞水通道蛋白5表达的影响及调控.细胞生物学杂志.2008,30：771-775.
15.陈学军,杨建华,郑伟.拓扑替康对卵巢癌SKOV3细胞水通道蛋白5及NF-κB表达的影响.癌症,2009,28(8)：856-860.
16.李留霞,赵艳萍,文建国等.卵巢上皮性癌组织中水通道蛋白3的表达.郑州大学学报(医学版),2008,43(2)：329-332
17. Kang SK, Chae YK, Woo J, et al. Role of human aquaporin 5 in colorectal carcinogenesis. Am J Pathol.2008,173(2):518-25.
18. Hiranmoy Bhattacharjee, Barry P Rosen, Rita Mukhopadhyay. Aquaglyceroporins and metalloid transport:Implication in human diseases. Handb Exp Pharmacol, 2009,190:309-325.
19. Jordy Leung, Annie Pang, Wai-Hung Yuen et al. Relationship of expression of aquaglycer 9 with arsenic uptake and sensitivity in leukemia cells. Blood,2007, 109:740-746.
20. Naranmandura H, Ogra Y, Iwata K. Evidence for toxicity differences between inorganic arsenite and thioarsenicals in human bladder cancer cells. Toxicol Appl Pharmacol.2009 Jul 15;238(2):133-40.
21. Elizabeth M.Jablonski,M.Adrian Mattocks, Eugene Sololov et al. Decreased aquaporin expression leads to increased resistance to apoptosis in hepatocellular carcinoma. Cancer Lett,2007,250(1):36-46.
22. Adnan Dibas, Ming-Hui Yang, Joseph Bobich et al. Stress-induced changes in neuronal aquaporin-9 in a retinal ganglion cell-line. Pharmacological Research, 2007,55:378-384.
23. Arima H, Yamamoto N, Sobue K, et al. Hyperosmolar mannitol simulates expression of aquaporins 4 and 9 through a p38 mitogen-activated protein kinase-dependent pathway in rat astrocytes. J Biol Chem.2007,278(45):44525-34.
24. MM Gottesman, T Fojo, SE Bates. Multidrug resistance in cancer:role of ATP-dependent transporters. Nat Rev Cancer,2002(2):48-58.
25. Ying Huang, Wolfgang Sadee. Membrane transporters and channels in chemoresistance and sensitivity of tumors cells. Cancer letter,2006,239:168-182.
26. Woo J, Lee J, Kim MS, et al. The effect of aquaporin 5 overexpression on the Ras signaling pathway. Biochem Biophys Res Commun.2008,367(2):291-8)
27. Umenishi F, Schrier RW. Hypertonicity-induced aquaporin-1 (AQP1) expression is mediated by the activation of MAPK pathways and hypertonicity-responsive element in the AQP1 gene. J Biol Chem,2003,287(18):15765-15770.
28. Umenishi F, Schrier RW. Idengifacation and characterization of a novel hypertonicity-responsive element in the human aquaporin-1 gene. Biochem Biophys Res Commun,2002,292:771-775.
29. Pedersen PS, Braunstein TH, Jorhensen A, et al. Stimulation of aquaporin-5 and transepithelial water permeability in human airway epithelium by hyperosomic. Pfluger Arch,2007,453(6):777-75.
30. Arima H, Yamamoto N, Sobue, et al. Hyperosmolar mannitol stimulates expression of aquaporin4 and 9 through a p38 mitogen-activated protein kinase-dependent pathway in rat astrocytes. J Biol Chem,2003,278(45): 44525-44534
1. Verkman AS, Mitra AK. Structure and function of aquaporin water channels. Am J Physiol,2000,278:F13-F28.
2. Fulvio Magni, Gecilia Sarto, Davide Ticozzi, et al. Proteomic knowledge of human aquaporins. Proteomics,2006,6:5637-5649.
3. Gonen T, Walz T. The structure of aquaporins. Q Rev Biophys 2006,39:361-396.
4. Ishibashi K, Kuwahara M, Gu Y, et al. Cloning and functional expression of a new aquaporin (AQP9) abundantly expressed in the peripheral leukocytes per-meable to water and urea, but not to glycerol. Biochem Biophys Res Commun,1998,244: 268-274.
5. Aishima S, Kuroda Y, Nishihara Y, et al. Down-regulation of aquaporin-1 in intrahepatic cholangiocarcinoma is related to tumor progression and mucin expression. Hum Pathol,2007,38:1819-1825.
6. Warth A, Kroger S, Wolburg H. Redistribution of aquaporin-4 in human glioblastoma correlates with loss of agrin immunoreactivity from brain capillary basal laminae. Acta Neuropathol,2004,107:311-318.
7. Warth A, Simon P, Capper D, et al. Expression pattern of the water channel aquaporin-4 in human gliomas is associated with blood-brain barrier disturbance but not with patient survival. J Neurosci Res,2007,85:1336-1346.
8. Warth A, Mittelbronn M, Hulper P, et al. Expression of the water channel protein aquaporin-9 in malignant brain tumors. Appl Immunohistochem Mol Morphol, 2007,15:193-198.
9. Saadoun S, Papadopoulos MC, Davies DC, et al. Increased aquaporin 1 water channel expression in human brain tumours. Br J Cancer,2002,87:621-623.
10. Oshio K, Binder DK, Liang Y, et al. Expression of the aquaporin-1 water channel in human glial tumors. Neurosurgery,2005,56:375-381.
11. Endo M, Jain RK, Witwer B, et al. Water channel(aquaporin 1) expression and distribution in mammary carcinomas and glioblastomas. Microvasc Res,1999,58: 89-98.
12. Markert JM, Fuller CM, Gillespie GY, et al. Differential gene expression profiling in human brain tumors. Physiol Genomics,2001,5:21-33.
13. Jablonski EM, Mattocks MA, Sokolov E, et al. Decreased aquaporin expression leads to increased resistance to apoptosis in hepatocellular carcinoma. Cancer Lett, 2007,250:36-46.
14. Chen Y, Tachibana O, Oda M, et al. Increased expression of aquaporin 1 in human hemangioblastomas and its correlation with cyst formation. J Neurooncol,2006, 80:219-225.
15. Longatti P, Basaldella L, Orvieto E, et al. Aquaporin(s) expression in choroid plexus tumours. Pediatr Neurosurg,2006,42:228-233.
16. Liu YL, Matsuzaki T, Nakazawa T, et al. Expression of aquaporin 3 (AQP3) in normal and neoplastic lung tissues. Hum Pathol,2007,38:171-178.
17. Hoque MO, Soria JC, Woo J,et al. Aquaporin 1 is overexpressed in lung cancer and stimulates NIH-3T3 cell proliferation and anchorage- independent growth. Am J Pathol,2006,168:1345-1353.
18. Yang JH, Shi YF, Cheng Q, et al. Expression and localization of aquaporin-5 in the epithelial ovarian tumors. Gynecol Oncol,2006,100:294-299.
19. Lacroix L, Lazar V, Michiels S, et al. Follicular thyroid tumors with the PAX8-PPARgammal rear-rangement display characteristic genetic alterations. Am J Pathol,2005,167:223-231.
20. Kafe H, Verbavatz JM, Cochand-Priollet B, et al. Collecting duct carcinoma:an entity to be redefined? Virchows Arch,2004,445:637-640.
21. Takenawa J, Kaneko Y, Kishishita M, et al. Transcript levels of aquaporin 1 and carbonic anhydrase IV aspredictive indicators for prognosis of renal cell carcinoma patients after nephrectomy. Int J Cancer,1998,79:1-7.
22. Fischer H, Stenling R, Rubio C, et al. Differential expression of aquaporin 8 in human colonic epithelial cells and colorectal tumors. BMC Physiol,2001,1:1
23. Moon C, Soria JC, Jang SJ, et al. Involve-ment of aquaporins in colorectal carcinogenesis. Oncogene,2003,22:6699-6703.
24. Polverini PJ. Angiogenisis in health and disease:insights into basic mechanisms and therapeutic oppourunitics. J Dent Educ,2002,66(8):962-975.
25. Hara-Chikuma M, Verkman AS. Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption. Mol Cell Biol,2008,28(1):326-32.
26. Woo J, Lee J, Chae YK,et al. Overexpression of AQP5, a putative oncogene, promotes cell growth and transformation. Cancer Lett,2008,264(1):54-62.
27. Yang B, Folkcsson HG, Yang J, et al. Reduced osmotic water permeability of the peritoneal barrier in aquaporin-1 konckout mice. Am J Physiol,1999, 276(1):76-81.
28. Jie Hu and A. S. Verkman. Increased migration and metastatic potential of tumor cells expressing aquaporin water channels. The FASEB Journal.2006, 20:1892-1894.
29. Saadoun, S., Papadopoulos, M. C., Hara-Chikuma, M., Verkman, A. S. Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature,2005,434:786-792.
30. Yang JH, Shi YF, Chen XD, et al The influence of aquaporin-1 and microvessel density on ovarian carcinogenesis and ascites forma-tion. Int J Gyneeol Cancer 2006,16 suppl 1:400-405
31. Um enishi F, Schrier RW. Hypertonicity-induced aquaporin-1 expression is m ediated by the activation of M APK pathways and hypertonicity-responsive element in the AQP1 gene. J Biol Chem,2003,278(18):15765.
32. Hashido M, Ikeguchi M, Kidera A. Com parative simulations of aquaporin family:AQP1, AQPZ, AQPO and GIpF. FEBS Lett,2005,579:5549.
33. Nemeth Cahalan KL, Hall JE. pH and calcium regulate the water permeability of aquaporin 0. J Biol Chem,2000,275(10):6777-6782.
34. Nemeth Cahalan KL, Kalman K, Hall JE. Molecular basis of pH and Ca2+ regulation of aquaporin water permeability. J Gen Physiol,2004,123(5):573-580.
35. Fujita Y, Yamamoto N, Sobue K et al. Effect of mild hypothermia on the expression of aquaporin family in cultured rat astrocytes under hypoxic condition. Neurosci Res,2003,47(4):437-444.
36. Yamamoto N, Yoneda K, Asai K, et al. Alterations in the expression of the AQP family in cultured rat astrocytes during hypoxia and reoxygenation. Brain Res Mol Brain Res,2001,90(1):26-38.
37. Aoki K, Uchihara T, Tsuchiya K, et al. Alterations in the expression of AQP4 in human brain with infarction. Acta Neuropathol,2003,106(2):121-124.
38. Hayashi Y, Edwads NA, Proescholdt MA, et al. Regulation and function of aquaporin-1 in glioma cells. Neoplasia,2007,9(9):777-789.
39. Umenishi F, Schrier RW. Hypertonicity-induced aquaporin-1 (AQP1) expression is mediated by the activation of MAPK pathways and hypertonicity-responsive element in the AQP1 gene. J Biol Chem,2003,278(18):15765-15770.
40. Umenishi F, Schrier RW. Identification and characterization of a novel hypertonicity-resposive element in the human aquaporin-1 gene. Biochem Biophys Res Commun,2002,292(3):771-775.
41. Pedersen PS, Braunstein TH, Jorgensen A, et al. Stimulation of aquaporin-5 and transepithelial water permeability in human airway epithelium by hyperosmotic stress. Pfluger Arch,2007,453(6):777-785.
42. Arima H, Yamamoto N, Sobue K, et al. Hyperosmolar mannitol stimulates expression of aquaporins 4 and 9 through a p38 mitogen-activated protein kinase-dependent pathway in rat astrocytes. J Biol Chem,2003,278(45): 44525-44534.
43. Maeno E, Ishizaki Y, Kanaseki T et al. Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis. Proc Natl Acad Sci USA,2000,97(17):9487-9492.
44. Bortner CD, Gomez—Angelats M, Cidlowski JA. Plasma membrane depolarization without repolarization is an early molecular event in anti—Fas induced apoptosis. J Biol Chem,2001,276(6):4304-4314.
45. Lee W K, Thevenod F. A role for mitochondrial aquaporins celluar life-and—death decision? Am J Physiol Cell Physio,2006,291(2):C195-C202.
46. Nobel CS, Aronson JK, van den Dobbelsteen DJ, et al. Inhibition of Na/K-ATPase may be one mechanis contributing to potassium efflux and cell shrinkage in CD9 induced apoptosis. Apoptosis,2000,5(2):153-163.
47. Hughes FM Jr, Bortner CD, Purdy GP, et al. Intracellular K suppresses the activation of apoptosis in lymphocytes. J Biol Chem,1997,272(48):30567-30576.
48. Jablonski EM, Webb AN, McConnell NA, et al. Plasma m embrane aquaporin activity can affect the rate of apoptosis but is inhibited after apoptotic volume decrease[J]. Am J Physiol Cell Physiol,2004,286(4):C975-C985.
49. Jablonski EM, Mattocks MA, Sokolov E, et al. Decreased aquaporin expression lcads to increased resistance to apoptosis in hepatocellular carcinoma. Cancer Letters,2007,250(1):36-46.
1. Linton KJ. Structure and function of ABC transporters. Physiology (Bethesda), 2007,22(2):122-130.
2. Ambudkar SV, Kim IW, Sauna ZE. The power of the pump:mechanisms of action of P-glycoprotein (ABCB1). Eur J Pharm Sci,2006,27(5):392-400.
3. Y. Huang, P. Anderle, K.J. Bussey, et al. Membrane Transporters and Channels: Role of the Transportome in Cancer Chemosensitivity and Chemoresistance, Cancer Res,2004,64:4294-4301.
4. S.V. Ambudkar, C. Kimchi-Sarfaty, Z.E. Sauna, et al. P-glycoprotein:from genomics to mechanism, Oncogene,2003,22:7468-7485.
5. Z.S. Chen, T. Furukawa, T. Sumizawa, et al. ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P, Mol Pharmacol,1999,55:921-928.
6. E.M. Leslie, R.G. Deeley, S.P. Cole. Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters, Toxicology,2001, 167:3-23.
7. S.P. Cole, G Bhardwaj, J.H. Gerlach, et al. Mao Q, Unadkat JD. Role of the breast cancer resistance protein(ABCG2) in drug transport. AAPS J,2005,7(1):118-157.
8. L.A. Doyle, W. Yang, L.V. Abruzzo, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells, Proc. Natl. Acad. Sci. USA,1998,95: 15665-15670.
9. R. Allikmets, L.M. Schriml, A. Hutchinson, et al. A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance, Cancer Res,1998,58:5337-5339.
10. B. Vulevic, Z. Chen, J.T. Boyd, et al. Cloning and characterization of human adenosine 5'-triphosphate-binding cassette, sub-family A,transporter 2 (ABCA2). Cancer Res,2001,61:3339-3347.
11. R. Boonstra, H. Timmer-Bosscha, J. van Echten-Arends, et al. Mitoxan-trone resistance in a small cell lung cancer cell line is associated with ABCA2 upregulation, Br J Cancer,2004,90:2411-2417.
12. A.J. Smith, A. van Helvoort, G van Meer, et al., MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping. J Biol Chem.2000,275:23530-23539.
13. G.D. Kruh, M.G Belinsky. The MRP family of drug efflux pumps. Oncogene,2003, 22:7537-7552.
14. Y. Guo, E. Kotova, Z.S. Chen, et al. Hopper-Borge, M.G Belinsky, et al., MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2',3'-dideoxycytidine and 9'-(2'-phosphonyl- methoxyethyl)adenine. J Biol Chem.2003,278:29509-29514.
15.M.A. Hediger, M.F. Romero, J.B. Peng, et al. The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteinsIntroduction. Pflugers Arch,2004,447:465-468.
16. S.C. Wong, S.A. Proefke, A. Bhushan, et al. Isolation of human cDNAs that restore methotrexate sensitivity and reduced folate carrier activity in methotrexate transport-defective Chinese hamster ovary cells. J Biol Chem,1995,270: 17468-17475.
17. V. Ganapathy, S.B. Smith, P.D. Prasad, SLC19:the folate/thiamine transporter family. Pflugers Arch.2004,447:641-646.
18. S. Liu, H. Huang, X. Lu, et al. Down-regulation of thiamine transporter THTR2 gene expression in breast cancer and its association with resistance to apoptosis. Mol Cancer Res,2003,1:665-673.
19. J.H. Gray, R.P. Owen, K.M. Giacomini. The concentrative nucleoside transporter family, SLC28. Pflugers Arch,2004,447:728-734.
20. J.R. Mackey, S.Y. Yao, K.M. Smith, et al. Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst,1999,91:1876-1881.
21. J.H. Gray, L.M. Mangravite, R.P. Owen, et al. Functional and genetic diversity in the concentrative nucleoside transporter, CNT1, in human populations. Mol Pharmacol,2004,65:512-519.
22. M.W. Ritzel, A.M. Ng, S.Y. Yao, et al. Molecular identification and character-ization of novel human and mouse concentrative NaC-nucleoside cotransporter proteins (hCNT3 and mCNT3)broadly selective for purine and pyrimidine nucleosides. J Biol Chem.2001,276:2914-2927.
23. S.A. Baldwin, P.R. Beal, S.Y. Yao, et al. The equilibrative nucleoside transporter family, SLC29. Pflugers Arch,2004,447:735-743.
24. D.R. Rauchwerger, P.S. Firby, D.W. Hedley, et al. Equilibrative-sensitive nucleoside transporter and its role in gemcitabine sensitivity. Cancer Res,2000, 60:6075-6079.
25. S.A. Baldwin, J.R. Mackey, C.E. Cass, et al. Nucleoside transporters:molecular biology and implications for therapeutic development. Mol Med Today,1999, 5:216-224.
26. J. Lin, D.A. Raoof, D.G Thomas, et al. L-type amino acid transporter-1 overexpression and melphalan sensitivity in Barrett's adenocarcinoma. Neoplasia, 2004,6:4-84.
27. H. Uchino, Y. Kanai, K. Kim do, et al. Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1):insights into the mechanisms of substrate recognition. Mol Pharmacol,2002,61:729-737.
28. Y. Kanai, H. Endou. Functional properties of multispecific amino acid transporters and their implications to transporter-mediated toxicity. J Toxicol Sci,2003, 28:1-17.
29. C.A. Wagner, F. Lang, S. Broer. Function and structure of heterodimeric amino acid transporters. Am J Physiol Cell Physiol,2001,281:C1077-C1093.
30. H. Sato, M. Tamba, K. Kuriyama-Matsumura, et al. Molecular cloning and expression of human xCT, the light chain of amino acid transport system xc. Antioxid Redox Signal,2000,2:665-671.
31. Y. Huang, Z. Dai, C. Barbacioru, et al. Cystine/gluta-mate transporter SLC7A11 in cancer chemosensitivity and resistance. Cancer Res,2005,65(16):7446-54.
32. S. Ishida, J. Lee, D.J. Thiele. Herskowitz, Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctrl in yeast and mammals. Proc Natl Acad Sci USA,2002,99:14298-14302.
33. A.K. Holzer, K. Katano, L.W. Klomp,et al. Cisplatin rapidly down-regulates its own infflux transporter hCTRl in cultured human ovarian carcinoma cells. Clin Cancer Res,2004,10:6744-6749.
34. Komatsu M, Sumizawa T, Motoh M, et al. Copper-transporting P-type adenosine triphosphatase(ATP7B) is associated with cisplatin resistance. Cancer Res,2000, 60:1312-1316.
35. Samimi G, Varki NM, Wilczynski S, et al. Increase in expression of the copper transporter ATP7A during platinum drug-based treatment is associated with poor survival in ovarian cancer patients. Clin Cancer Res,2003,9:5853-5859.
36. N.N. Danial, C.F. Gramm, L. Scorrano, et al. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis, Nature,2003, 424:952-956.
37. M. Veyhl, K. Wagner, C. Volk, et al. Transport of the new chemo-therapeutic agent beta-D-glucosylisophosphoramide mustard (D-19575) into tumor cells is mediated by the NaC-D-glucose cotransporter SAAT1. Proc Natl Acad Sci USA,1998, 95:2914-2919.
38. H. Daniel, G. Kottra. The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology. Pflugers Arch,2004,447:610-618.
39. B.E. Enerson, L.R. Drewes. Molecular features, regulation, and function of monocarboxylate transporters:implications for drug delivery. J Pharm Sci,2003, 92:1531-1544.
40. R. Chen, J.A. Nelson. Role of organic cation transporters in the renal secretion of nucleosides. Biochem Pharmacol,2000,60:215-219.
41. Chen SZ, Jiang M, Zhen YS. Correlation of HE RG K channel protein expression to chemosensitivity of tumor cells to doxoru bicin and its modulation by erythromycin. Ai Zheng,2005,24:924-929.
42. Vaalburg W, Hendrikse NH, Elsinga PH, et al. P-glycoprotein activity and biological and biological response. Toxicol Appl Pharmacol,2005,207:257-260.
43. Ise T, Shimizu T, Lee EL, et al. Roles of volume-sensitive Cl Channel in cisplatin-induced apoptosis in human epidermoid cancer cells. J Membr Biol, 2005,(3):139-145.
44. Sun D, Lennernas H, Welage LS, et al. Comparison of human duodenum and Caco-2 gene expression profiles for 120000 gene sequences tags and correlation with permeability of 26 drugs. Pharm Res,2002,19:1400-1416.
45. Woo J, Lee J, Kim MS, et al. The effect of aquaporin 5 overexpression on the Ras signaling pathway. Biochem Biophys Res Commun.2008,367(2):291
46. Hiranmoy Bhattacharjee, Barry P Rosen, Rita Mukhopadhyay. Aquaglyceroporins and metalloid transport:Implication in human diseases. Handb Exp Pharmacol, 2009,190:309-325.
47. Jordy Leung, Annie Pang, Wai-Hung Yuen et al. Relationship of expression of aquaglycer 9 with arsenic uptake and sensitivity in leukemia cells. Blood,2007, 109:740-746.
48. Nestor L. Uzcategui, Yao Zhou, Katherine Figarella, et al. Alteration in glycerol and metalloid permeability by a single mutation in the extracellular C-loop of Leishmania major aquaglyceroporin LmAQPl. Mol Microbiol,2008,70(6): 1365-2958.
49. Naranmandura H, Ogra Y, Iwata K. Evidence for toxicity differences between inorganic arsenite and thioarsenicals in human bladder cancer cells. Toxicol Appl Pharmaco,2009,238(2):133-40.
2. Fulvio Magni, Gecilia Sarto, Davide Ticozzi, et al. Proteomic knowledge of human aquaporins. Proteomics,2006,6:5637-5649。
3. Gonen T, Walz T. The structure of aquaporins. Q Rev Biophys 2006,39:361-396.
4. Ishibashi K, Kuwahara M, Gu Y, et al. (1998) Cloning and functional expression of a new aquaporin (AQP9) abundantly expressed in the peripheral leukocytes per-meable to water and urea, but not to glycerol. Biochem Biophys Res Commun, 1998,244:268-274.
5. M.C Papadopoulos, S.Saadoun, A.S Verkman. Aquaporins and cell migration. Pflugers Arch-Eur J Physiol,2008,456:693-700.
6. Hibuse T, Maeda N, Nagasawa A, et al. Aquaporins and glycerol metabolism. Biochimica Biophysica Acta,2006,1758:1004-1011.
7. Mobasheri A, Airlew R, Hewitt SM, et al. Heterogeneous expression of the aquaporin1(AQP1)water channel in tumors of the prostate, breast, ovary, colon and lung:a study using high density multiple human tumor tissue mocroarrays. Int J Oncol,2005,26:1149-1158.
8. Yang JH, Shi YF, Chen XD et al. The influence of aquaporin-1 and microvessel density on ovarian carcinogenesis and ascites formation Int J Gynecol Cancer 2006;16(Suppl, 1):400-405.
9.杨建华,石一复,程琪等.卵巢上皮性肿瘤患者AQP1蛋白及mRNA的表达及意义.中华妇产科杂志,2005,40(9)：623-626.
10. Yang JH, Shi YF, Chen Q et al. Expression and localization of aquaporin-5 in the epithelial ovarian tumor. Gynecologic Oncology,2006,100 (2):294-299.
11.李留霞,赵艳萍,文建国等.卵巢上皮性癌组织中水通道蛋白3的表达.郑州大学学报(医学版),2008,43(2)：329-332.
12. Agre P, King LS, Yasui M, et al. Aquaporin water channels-from atomic structure to clinical medicine. J Physiol,2002,542:3-16
13. A.S Verkman, Mariko Hara-Chikuma. Aquaporins-new players in cancer biology. J Mol Med,2008,86:523-529
14. Eric Mccoy, Harald Sontheimer. Expression and function of water channels (Aquaporins) in migration malignant astrocytes. Glia,2007 55:1034-1043.
15. Young Kwang Chae, Janghee Woo, Mi-Jung Kim, et al. Expression of aquaporin 5 promotes tumor invasion in human non small cell lung cancer. Plos ONE,2008, 5(2162):1-9.
16. Yasui M, Hazama A, Kwon TH, et al. Rapid gating and anion permeability of an intracellular aquaporin. Nature 1999,402(6758):184-187.
17. Yasui M. pH regulated anion permeability of aquaporin-6. Handb Exp Pharmacol. 2009, (190):299-308.
18. Hazama A, Kozono D, Guggino WB, et al. Ion permea-tion of AQP6 water channel protein. Single channel record-ings after Hg2+ activation. J Biol Chem 2002,277(32):29224-29230.
19. Ikeda M, Beitz E, Kozono D, et al. Charac-terization of aquaporin-6 as a nitrate channel in mammalian cells. Requirement of pore-lining residue threonine 63. J Biol Chem 2002,277(42):39873-39879.
20. Liu K, Kozono D, Kato Y, et al. Conversion of aquaporin 6 from an anion channel to a water-selective channel by a single amino acid substitution. Proc Natl Acad Sci USA,2005,102(6):2192-2197.
21. Yasui M, Kwon TH, Knepper MA, et al. Aquaporin-6:An intracellular vesicle water channel protein in renal epithelia. Proc Natl Acad Sci USA 1999,96(10): 5808-5813.
22. Nagase H, Agren J, Saito A, et al. Molec-ular cloning and character- ization of mouse aquaporin 6. Bio-chem Biophys Res Commun 2007,352(1):12-16.
23. Lopez IA, Ishiyama G, Lee M, et al. Immunohisto-chemical localization of aquaporins in the human inner ear.Cell Tissue Res 2007,328(3):453-460.
24. Matsuki-Fukushima M, Hashimoto S, Shimono M, et al. Presence and localization of aquaporin-6 in rat parotid acinar cells. Cell Tissue Res 2008,332(1):73-80.
25. Umberto L, Giulia G, Mariarosa P, et al. Aquaporin-6 is expression along the rat gastrointestinal tract and upregulated by feeding in the small intestine. BMC Physiology,2009,9:18.
26. Jablonski EM, Mattocks MA, Sokolov E et al. Decreased aquaporin expression leads to increased resistance to apoptosis in hepatocellular carcinoma. Cancer Lett. 2007,250(1):36-46.
27. Matsuzaki T, Tajika Y, Tserentsoodol N, et al. Aquaporins:a water channel family. Anat Sci Int,2002,77(2):85-93.
28. Wang S, Chen J, Katherine T, et al. Expression of aquaporin-8 and its up-regulation by cyclic adenosine monophosphate in human WISH cells. Am J Obstet Gynecol,2003,188:997-1001.
29. Mock N, McConnell NA, Hughes FM. Potential role of aquaporins in the formation and expansion of the ovarian follicular antrum and their regulation by gonadotropins. Recent research developments in endocrinology,2004,4 (1): 169-179.
30. Calamita G, Ferri D, Gena P, et al. The inner mitochondrial membrane has aquaporin-8 water channels and is hishly permeable to water. Journal of Biological Chemistry,2005,280(17):17149-17153.
31. Gonen T, Walz T. The structure of aquaporins. Q Rev Biophys 2006,39:361-396.
32. Tsukaguchi H, Weremowicz S, Morton CC, et al. Functional and molecular characterization of the human neutral solute channel aquaporin-9. Am J Physiol, 1999,277:F685-F696.
33. Ishibashi K, Kuwahara M, Gu Y, et al. Cloning and functional expression of a new aquaporin (AQP9) abundantly expressed in the peripheral leukocytes per-meable to water and urea, but not to glycerol. Biochem Biophys Res Commun,1998,244: 268-274.
34. Tsukaguchi H, Weremowicz S, Morton CC, et al. Functional and molecular characterization of the human neutral solute channel aquaporin-9. Am J Physiol, 1999,277:F685-F696.
35. Tsukaguchi H, Shayakul C, Berger UV, et al. Molecular characterization of a broad selectivity neutral solute channel. J Biol Chem,1998 273:24737-24743.
36. Holm LM, Jahn TP, Moller AL, et al. NH3 and NH4 permeability in aquaporin
-expressing Xenopus oocytes. Pflugers Arch,2005,450:415-428.
37. Ko SB, Uchida S, Naruse S, et al. Cloning and functional expression of rAOP9L a new member of aquaporin family from rat liver. Biochem Mol Biol Int,1999, 47:309-318.
38. Elkjaer M, Vajda Z, Nejsum LN, et al. Immunolocalization of AQP9 in liver, epididymis, testis, spleen, and brain. Biochem Biophys Res Commun,2000,276: 1118-1128
39. Badaut J, Hirt L, Granziera C, et al. Astrocyte-specific expression of aquaporin-9 in mouse brain is increased after transient focal cerebral ischemia. J Cereb Blood Flow Metab,2001,21:477-482.
40. Badaut J, Petit JM, Brunet JF, et al. Distribution of aquaporin 9 in the adult rat brain preferential expression in catecholaminergic neurons and in glia cells. Neuroscience,2004,128:27-38.
41. Oshio K, Binder DK, Yang B, et al. Expression of aquaporin water channels in mouse spinal cord. Neuroscience,2004,127:685-693.
42. Pastor-Soler N, Isnard-Bagnis C, Herak-Kramberger C et al. Expression of aquaporin 9 in the adult rat epididymal epithelium is modulated by androgens. Biology of Reproduction,2002,66:1716-1722.
43.刘絮,张忠芳,赵丹等.不同发育阶段大鼠睾丸水通道蛋白AQP9的表达研究.北华大学学报,2004,5：509-511.
44. Beall MH, van den Wijngaard JP, van Gemert MJ, et al. Regulation of amniotic fluid volume. Placenta,2007,28:824-32.
45. Wang S, Chen J, Huang B, et al. Cloning and cellular expression of aquaporin 9 in ovine fetal membranes. Am J Obstet Gynecol 2005,193:841-8.
46. Damiano A, Zotta E, Goldstein J, et al. Water channel proteins AQP3 and AQP9 are present in syncytiotrophoblast of human term placenta. Placenta,2001, 22:776-81.
47. de Castro Ribeiro M, Hirt L, Bogousslavsky J, et al. Time course of aquaporin expression after transient focal cerebral ischemia in mice. J Neurosci Res,2006, 83:1231-1240.
48. Leung J, Pang A, Yuen WH, et al. Relationship of expression of aqua-glyceroporin 9 with arsenic uptake and sensitivity in leukemia cells. Toxicol In Vitro.2009, 23(2):209-16.
49. Warth A, Mittelbronn M, Hulper P, et al. Expression of the water channel protein aquaporin-9 in malignant brain tumors. Appl Immunohistochem Mol Morphol. 2007,15(2):193-8.
1. A.S Verkman, Mariko Hara-Chikuma. Aquaporins-new players in cancer biology. J Mol Med,2008,86:523-529
2. Saadoun S, Papadopoulous MC et al. Increased aquaporin 1 water channel expression in human brain tumors. Br J Cancer.2002,87(6):621-623.
3. Saadoun S, Papadopoulous MC et al. Aquaporin-4 expression is increased in oedematous human brain tumors. J Neurol Neurosurg Psychiatry.2002, 72(2):262-265
4. Hara-Chikuma M, Verkman AS. Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption. Mol Cell Biol.2008,28(1):326-32.
5. Huang Y, Murakami T, Sano F. Expression of Aquaporin 1 in Primary Renal Tumors:A Prognostic Indicator for Clear-Cell Renal Cell Carcinoma. Eur Urol. 2008 Oct 14.
6. Fischer H, Stenling R, Carlos B, et al. Differential expression of aquaporin 8 in human colonic epithelial cells and colorectal tumors. BMC Physic.2001,1:1
7. Moon C, Soria JC, Jaug SJ, et al. Involvement of aquaporins in colreetal omeinogenesis. Oncogene.2003,22(43):6699-6703.
8. Hoque MO, Soria JC, Woo J, et al. Aquaporin 1 is overexpressed in lung cancer and stimulates NIH-3T3 cell proliferation and anchorage-independent growth. Am J Pathol.2006,168(4):1345-53.
9. Chae YK, Woo J, Kim MJ et al. Expression of aquaporin 5 (AQP5) promotes tumor invasion in human non small cell lung cancer. PLoS ONE.2008, 14;3(5):e2162.
10. Eric Mccoy, Harald Sontheimer. Expression and function of water channels (Aquaporins) in migration malignant astrocytes. Glia 2007 55:1034-1043.
11. Young Kwang Chae, Janghee Woo, Mi-Jung Kim, et al. Expression of aquaporin 5 promotes tumor invasion in human non small cell lung cancer. Plos ONE,2008, 5(2162):1-9.
12. Yang JH, Shi YF, Cheng Q, et al. Expression and localization of aquaporin-5 in the epithelial ovarian tumor. Gynecologic Oncology.2006,100(2):294-299
13. Yang JH, Shi YF, Chen XD, Qi WJ. The influence of aquaporin-1 and microvessel density on ovarian carcinogenesis and ascites formation. Int J Gynecol Cancer. 2006,16(Suppl.):400-405
14.杨建华,郑伟,石一复,陈学军.顺铂对卵巢癌SKOV3细胞水通道蛋白5表达的影响及调控.细胞生物学杂志.2008,30：771-775.
15.陈学军,杨建华,郑伟.拓扑替康对卵巢癌SKOV3细胞水通道蛋白5及NF-κB表达的影响.癌症,2009,28(8)：856-860.
16.李留霞,赵艳萍,文建国等.卵巢上皮性癌组织中水通道蛋白3的表达.郑州大学学报(医学版),2008,43(2)：329-332
17. Kang SK, Chae YK, Woo J, et al. Role of human aquaporin 5 in colorectal carcinogenesis. Am J Pathol.2008,173(2):518-25.
18. Hiranmoy Bhattacharjee, Barry P Rosen, Rita Mukhopadhyay. Aquaglyceroporins and metalloid transport:Implication in human diseases. Handb Exp Pharmacol, 2009,190:309-325.
19. Jordy Leung, Annie Pang, Wai-Hung Yuen et al. Relationship of expression of aquaglycer 9 with arsenic uptake and sensitivity in leukemia cells. Blood,2007, 109:740-746.
20. Naranmandura H, Ogra Y, Iwata K. Evidence for toxicity differences between inorganic arsenite and thioarsenicals in human bladder cancer cells. Toxicol Appl Pharmacol.2009 Jul 15;238(2):133-40.
21. Elizabeth M.Jablonski,M.Adrian Mattocks, Eugene Sololov et al. Decreased aquaporin expression leads to increased resistance to apoptosis in hepatocellular carcinoma. Cancer Lett,2007,250(1):36-46.
22. Adnan Dibas, Ming-Hui Yang, Joseph Bobich et al. Stress-induced changes in neuronal aquaporin-9 in a retinal ganglion cell-line. Pharmacological Research, 2007,55:378-384.
23. Arima H, Yamamoto N, Sobue K, et al. Hyperosmolar mannitol simulates expression of aquaporins 4 and 9 through a p38 mitogen-activated protein kinase-dependent pathway in rat astrocytes. J Biol Chem.2007,278(45):44525-34.
24. MM Gottesman, T Fojo, SE Bates. Multidrug resistance in cancer:role of ATP-dependent transporters. Nat Rev Cancer,2002(2):48-58.
25. Ying Huang, Wolfgang Sadee. Membrane transporters and channels in chemoresistance and sensitivity of tumors cells. Cancer letter,2006,239:168-182.
26. Woo J, Lee J, Kim MS, et al. The effect of aquaporin 5 overexpression on the Ras signaling pathway. Biochem Biophys Res Commun.2008,367(2):291-8)
27. Umenishi F, Schrier RW. Hypertonicity-induced aquaporin-1 (AQP1) expression is mediated by the activation of MAPK pathways and hypertonicity-responsive element in the AQP1 gene. J Biol Chem,2003,287(18):15765-15770.
28. Umenishi F, Schrier RW. Idengifacation and characterization of a novel hypertonicity-responsive element in the human aquaporin-1 gene. Biochem Biophys Res Commun,2002,292:771-775.
29. Pedersen PS, Braunstein TH, Jorhensen A, et al. Stimulation of aquaporin-5 and transepithelial water permeability in human airway epithelium by hyperosomic. Pfluger Arch,2007,453(6):777-75.
30. Arima H, Yamamoto N, Sobue, et al. Hyperosmolar mannitol stimulates expression of aquaporin4 and 9 through a p38 mitogen-activated protein kinase-dependent pathway in rat astrocytes. J Biol Chem,2003,278(45): 44525-44534
1. Verkman AS, Mitra AK. Structure and function of aquaporin water channels. Am J Physiol,2000,278:F13-F28.
2. Fulvio Magni, Gecilia Sarto, Davide Ticozzi, et al. Proteomic knowledge of human aquaporins. Proteomics,2006,6:5637-5649.
3. Gonen T, Walz T. The structure of aquaporins. Q Rev Biophys 2006,39:361-396.
4. Ishibashi K, Kuwahara M, Gu Y, et al. Cloning and functional expression of a new aquaporin (AQP9) abundantly expressed in the peripheral leukocytes per-meable to water and urea, but not to glycerol. Biochem Biophys Res Commun,1998,244: 268-274.
5. Aishima S, Kuroda Y, Nishihara Y, et al. Down-regulation of aquaporin-1 in intrahepatic cholangiocarcinoma is related to tumor progression and mucin expression. Hum Pathol,2007,38:1819-1825.
6. Warth A, Kroger S, Wolburg H. Redistribution of aquaporin-4 in human glioblastoma correlates with loss of agrin immunoreactivity from brain capillary basal laminae. Acta Neuropathol,2004,107:311-318.
7. Warth A, Simon P, Capper D, et al. Expression pattern of the water channel aquaporin-4 in human gliomas is associated with blood-brain barrier disturbance but not with patient survival. J Neurosci Res,2007,85:1336-1346.
8. Warth A, Mittelbronn M, Hulper P, et al. Expression of the water channel protein aquaporin-9 in malignant brain tumors. Appl Immunohistochem Mol Morphol, 2007,15:193-198.
9. Saadoun S, Papadopoulos MC, Davies DC, et al. Increased aquaporin 1 water channel expression in human brain tumours. Br J Cancer,2002,87:621-623.
10. Oshio K, Binder DK, Liang Y, et al. Expression of the aquaporin-1 water channel in human glial tumors. Neurosurgery,2005,56:375-381.
11. Endo M, Jain RK, Witwer B, et al. Water channel(aquaporin 1) expression and distribution in mammary carcinomas and glioblastomas. Microvasc Res,1999,58: 89-98.
12. Markert JM, Fuller CM, Gillespie GY, et al. Differential gene expression profiling in human brain tumors. Physiol Genomics,2001,5:21-33.
13. Jablonski EM, Mattocks MA, Sokolov E, et al. Decreased aquaporin expression leads to increased resistance to apoptosis in hepatocellular carcinoma. Cancer Lett, 2007,250:36-46.
14. Chen Y, Tachibana O, Oda M, et al. Increased expression of aquaporin 1 in human hemangioblastomas and its correlation with cyst formation. J Neurooncol,2006, 80:219-225.
15. Longatti P, Basaldella L, Orvieto E, et al. Aquaporin(s) expression in choroid plexus tumours. Pediatr Neurosurg,2006,42:228-233.
16. Liu YL, Matsuzaki T, Nakazawa T, et al. Expression of aquaporin 3 (AQP3) in normal and neoplastic lung tissues. Hum Pathol,2007,38:171-178.
17. Hoque MO, Soria JC, Woo J,et al. Aquaporin 1 is overexpressed in lung cancer and stimulates NIH-3T3 cell proliferation and anchorage- independent growth. Am J Pathol,2006,168:1345-1353.
18. Yang JH, Shi YF, Cheng Q, et al. Expression and localization of aquaporin-5 in the epithelial ovarian tumors. Gynecol Oncol,2006,100:294-299.
19. Lacroix L, Lazar V, Michiels S, et al. Follicular thyroid tumors with the PAX8-PPARgammal rear-rangement display characteristic genetic alterations. Am J Pathol,2005,167:223-231.
20. Kafe H, Verbavatz JM, Cochand-Priollet B, et al. Collecting duct carcinoma:an entity to be redefined? Virchows Arch,2004,445:637-640.
21. Takenawa J, Kaneko Y, Kishishita M, et al. Transcript levels of aquaporin 1 and carbonic anhydrase IV aspredictive indicators for prognosis of renal cell carcinoma patients after nephrectomy. Int J Cancer,1998,79:1-7.
22. Fischer H, Stenling R, Rubio C, et al. Differential expression of aquaporin 8 in human colonic epithelial cells and colorectal tumors. BMC Physiol,2001,1:1
23. Moon C, Soria JC, Jang SJ, et al. Involve-ment of aquaporins in colorectal carcinogenesis. Oncogene,2003,22:6699-6703.
24. Polverini PJ. Angiogenisis in health and disease:insights into basic mechanisms and therapeutic oppourunitics. J Dent Educ,2002,66(8):962-975.
25. Hara-Chikuma M, Verkman AS. Prevention of skin tumorigenesis and impairment of epidermal cell proliferation by targeted aquaporin-3 gene disruption. Mol Cell Biol,2008,28(1):326-32.
26. Woo J, Lee J, Chae YK,et al. Overexpression of AQP5, a putative oncogene, promotes cell growth and transformation. Cancer Lett,2008,264(1):54-62.
27. Yang B, Folkcsson HG, Yang J, et al. Reduced osmotic water permeability of the peritoneal barrier in aquaporin-1 konckout mice. Am J Physiol,1999, 276(1):76-81.
28. Jie Hu and A. S. Verkman. Increased migration and metastatic potential of tumor cells expressing aquaporin water channels. The FASEB Journal.2006, 20:1892-1894.
29. Saadoun, S., Papadopoulos, M. C., Hara-Chikuma, M., Verkman, A. S. Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature,2005,434:786-792.
30. Yang JH, Shi YF, Chen XD, et al The influence of aquaporin-1 and microvessel density on ovarian carcinogenesis and ascites forma-tion. Int J Gyneeol Cancer 2006,16 suppl 1:400-405
31. Um enishi F, Schrier RW. Hypertonicity-induced aquaporin-1 expression is m ediated by the activation of M APK pathways and hypertonicity-responsive element in the AQP1 gene. J Biol Chem,2003,278(18):15765.
32. Hashido M, Ikeguchi M, Kidera A. Com parative simulations of aquaporin family:AQP1, AQPZ, AQPO and GIpF. FEBS Lett,2005,579:5549.
33. Nemeth Cahalan KL, Hall JE. pH and calcium regulate the water permeability of aquaporin 0. J Biol Chem,2000,275(10):6777-6782.
34. Nemeth Cahalan KL, Kalman K, Hall JE. Molecular basis of pH and Ca2+ regulation of aquaporin water permeability. J Gen Physiol,2004,123(5):573-580.
35. Fujita Y, Yamamoto N, Sobue K et al. Effect of mild hypothermia on the expression of aquaporin family in cultured rat astrocytes under hypoxic condition. Neurosci Res,2003,47(4):437-444.
36. Yamamoto N, Yoneda K, Asai K, et al. Alterations in the expression of the AQP family in cultured rat astrocytes during hypoxia and reoxygenation. Brain Res Mol Brain Res,2001,90(1):26-38.
37. Aoki K, Uchihara T, Tsuchiya K, et al. Alterations in the expression of AQP4 in human brain with infarction. Acta Neuropathol,2003,106(2):121-124.
38. Hayashi Y, Edwads NA, Proescholdt MA, et al. Regulation and function of aquaporin-1 in glioma cells. Neoplasia,2007,9(9):777-789.
39. Umenishi F, Schrier RW. Hypertonicity-induced aquaporin-1 (AQP1) expression is mediated by the activation of MAPK pathways and hypertonicity-responsive element in the AQP1 gene. J Biol Chem,2003,278(18):15765-15770.
40. Umenishi F, Schrier RW. Identification and characterization of a novel hypertonicity-resposive element in the human aquaporin-1 gene. Biochem Biophys Res Commun,2002,292(3):771-775.
41. Pedersen PS, Braunstein TH, Jorgensen A, et al. Stimulation of aquaporin-5 and transepithelial water permeability in human airway epithelium by hyperosmotic stress. Pfluger Arch,2007,453(6):777-785.
42. Arima H, Yamamoto N, Sobue K, et al. Hyperosmolar mannitol stimulates expression of aquaporins 4 and 9 through a p38 mitogen-activated protein kinase-dependent pathway in rat astrocytes. J Biol Chem,2003,278(45): 44525-44534.
43. Maeno E, Ishizaki Y, Kanaseki T et al. Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis. Proc Natl Acad Sci USA,2000,97(17):9487-9492.
44. Bortner CD, Gomez—Angelats M, Cidlowski JA. Plasma membrane depolarization without repolarization is an early molecular event in anti—Fas induced apoptosis. J Biol Chem,2001,276(6):4304-4314.
45. Lee W K, Thevenod F. A role for mitochondrial aquaporins celluar life-and—death decision? Am J Physiol Cell Physio,2006,291(2):C195-C202.
46. Nobel CS, Aronson JK, van den Dobbelsteen DJ, et al. Inhibition of Na/K-ATPase may be one mechanis contributing to potassium efflux and cell shrinkage in CD9 induced apoptosis. Apoptosis,2000,5(2):153-163.
47. Hughes FM Jr, Bortner CD, Purdy GP, et al. Intracellular K suppresses the activation of apoptosis in lymphocytes. J Biol Chem,1997,272(48):30567-30576.
48. Jablonski EM, Webb AN, McConnell NA, et al. Plasma m embrane aquaporin activity can affect the rate of apoptosis but is inhibited after apoptotic volume decrease[J]. Am J Physiol Cell Physiol,2004,286(4):C975-C985.
49. Jablonski EM, Mattocks MA, Sokolov E, et al. Decreased aquaporin expression lcads to increased resistance to apoptosis in hepatocellular carcinoma. Cancer Letters,2007,250(1):36-46.
1. Linton KJ. Structure and function of ABC transporters. Physiology (Bethesda), 2007,22(2):122-130.
2. Ambudkar SV, Kim IW, Sauna ZE. The power of the pump:mechanisms of action of P-glycoprotein (ABCB1). Eur J Pharm Sci,2006,27(5):392-400.
3. Y. Huang, P. Anderle, K.J. Bussey, et al. Membrane Transporters and Channels: Role of the Transportome in Cancer Chemosensitivity and Chemoresistance, Cancer Res,2004,64:4294-4301.
4. S.V. Ambudkar, C. Kimchi-Sarfaty, Z.E. Sauna, et al. P-glycoprotein:from genomics to mechanism, Oncogene,2003,22:7468-7485.
5. Z.S. Chen, T. Furukawa, T. Sumizawa, et al. ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P, Mol Pharmacol,1999,55:921-928.
6. E.M. Leslie, R.G. Deeley, S.P. Cole. Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters, Toxicology,2001, 167:3-23.
7. S.P. Cole, G Bhardwaj, J.H. Gerlach, et al. Mao Q, Unadkat JD. Role of the breast cancer resistance protein(ABCG2) in drug transport. AAPS J,2005,7(1):118-157.
8. L.A. Doyle, W. Yang, L.V. Abruzzo, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells, Proc. Natl. Acad. Sci. USA,1998,95: 15665-15670.
9. R. Allikmets, L.M. Schriml, A. Hutchinson, et al. A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance, Cancer Res,1998,58:5337-5339.
10. B. Vulevic, Z. Chen, J.T. Boyd, et al. Cloning and characterization of human adenosine 5'-triphosphate-binding cassette, sub-family A,transporter 2 (ABCA2). Cancer Res,2001,61:3339-3347.
11. R. Boonstra, H. Timmer-Bosscha, J. van Echten-Arends, et al. Mitoxan-trone resistance in a small cell lung cancer cell line is associated with ABCA2 upregulation, Br J Cancer,2004,90:2411-2417.
12. A.J. Smith, A. van Helvoort, G van Meer, et al., MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping. J Biol Chem.2000,275:23530-23539.
13. G.D. Kruh, M.G Belinsky. The MRP family of drug efflux pumps. Oncogene,2003, 22:7537-7552.
14. Y. Guo, E. Kotova, Z.S. Chen, et al. Hopper-Borge, M.G Belinsky, et al., MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2',3'-dideoxycytidine and 9'-(2'-phosphonyl- methoxyethyl)adenine. J Biol Chem.2003,278:29509-29514.
15.M.A. Hediger, M.F. Romero, J.B. Peng, et al. The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteinsIntroduction. Pflugers Arch,2004,447:465-468.
16. S.C. Wong, S.A. Proefke, A. Bhushan, et al. Isolation of human cDNAs that restore methotrexate sensitivity and reduced folate carrier activity in methotrexate transport-defective Chinese hamster ovary cells. J Biol Chem,1995,270: 17468-17475.
17. V. Ganapathy, S.B. Smith, P.D. Prasad, SLC19:the folate/thiamine transporter family. Pflugers Arch.2004,447:641-646.
18. S. Liu, H. Huang, X. Lu, et al. Down-regulation of thiamine transporter THTR2 gene expression in breast cancer and its association with resistance to apoptosis. Mol Cancer Res,2003,1:665-673.
19. J.H. Gray, R.P. Owen, K.M. Giacomini. The concentrative nucleoside transporter family, SLC28. Pflugers Arch,2004,447:728-734.
20. J.R. Mackey, S.Y. Yao, K.M. Smith, et al. Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst,1999,91:1876-1881.
21. J.H. Gray, L.M. Mangravite, R.P. Owen, et al. Functional and genetic diversity in the concentrative nucleoside transporter, CNT1, in human populations. Mol Pharmacol,2004,65:512-519.
22. M.W. Ritzel, A.M. Ng, S.Y. Yao, et al. Molecular identification and character-ization of novel human and mouse concentrative NaC-nucleoside cotransporter proteins (hCNT3 and mCNT3)broadly selective for purine and pyrimidine nucleosides. J Biol Chem.2001,276:2914-2927.
23. S.A. Baldwin, P.R. Beal, S.Y. Yao, et al. The equilibrative nucleoside transporter family, SLC29. Pflugers Arch,2004,447:735-743.
24. D.R. Rauchwerger, P.S. Firby, D.W. Hedley, et al. Equilibrative-sensitive nucleoside transporter and its role in gemcitabine sensitivity. Cancer Res,2000, 60:6075-6079.
25. S.A. Baldwin, J.R. Mackey, C.E. Cass, et al. Nucleoside transporters:molecular biology and implications for therapeutic development. Mol Med Today,1999, 5:216-224.
26. J. Lin, D.A. Raoof, D.G Thomas, et al. L-type amino acid transporter-1 overexpression and melphalan sensitivity in Barrett's adenocarcinoma. Neoplasia, 2004,6:4-84.
27. H. Uchino, Y. Kanai, K. Kim do, et al. Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1):insights into the mechanisms of substrate recognition. Mol Pharmacol,2002,61:729-737.
28. Y. Kanai, H. Endou. Functional properties of multispecific amino acid transporters and their implications to transporter-mediated toxicity. J Toxicol Sci,2003, 28:1-17.
29. C.A. Wagner, F. Lang, S. Broer. Function and structure of heterodimeric amino acid transporters. Am J Physiol Cell Physiol,2001,281:C1077-C1093.
30. H. Sato, M. Tamba, K. Kuriyama-Matsumura, et al. Molecular cloning and expression of human xCT, the light chain of amino acid transport system xc. Antioxid Redox Signal,2000,2:665-671.
31. Y. Huang, Z. Dai, C. Barbacioru, et al. Cystine/gluta-mate transporter SLC7A11 in cancer chemosensitivity and resistance. Cancer Res,2005,65(16):7446-54.
32. S. Ishida, J. Lee, D.J. Thiele. Herskowitz, Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctrl in yeast and mammals. Proc Natl Acad Sci USA,2002,99:14298-14302.
33. A.K. Holzer, K. Katano, L.W. Klomp,et al. Cisplatin rapidly down-regulates its own infflux transporter hCTRl in cultured human ovarian carcinoma cells. Clin Cancer Res,2004,10:6744-6749.
34. Komatsu M, Sumizawa T, Motoh M, et al. Copper-transporting P-type adenosine triphosphatase(ATP7B) is associated with cisplatin resistance. Cancer Res,2000, 60:1312-1316.
35. Samimi G, Varki NM, Wilczynski S, et al. Increase in expression of the copper transporter ATP7A during platinum drug-based treatment is associated with poor survival in ovarian cancer patients. Clin Cancer Res,2003,9:5853-5859.
36. N.N. Danial, C.F. Gramm, L. Scorrano, et al. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis, Nature,2003, 424:952-956.
37. M. Veyhl, K. Wagner, C. Volk, et al. Transport of the new chemo-therapeutic agent beta-D-glucosylisophosphoramide mustard (D-19575) into tumor cells is mediated by the NaC-D-glucose cotransporter SAAT1. Proc Natl Acad Sci USA,1998, 95:2914-2919.
38. H. Daniel, G. Kottra. The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology. Pflugers Arch,2004,447:610-618.
39. B.E. Enerson, L.R. Drewes. Molecular features, regulation, and function of monocarboxylate transporters:implications for drug delivery. J Pharm Sci,2003, 92:1531-1544.
40. R. Chen, J.A. Nelson. Role of organic cation transporters in the renal secretion of nucleosides. Biochem Pharmacol,2000,60:215-219.
41. Chen SZ, Jiang M, Zhen YS. Correlation of HE RG K channel protein expression to chemosensitivity of tumor cells to doxoru bicin and its modulation by erythromycin. Ai Zheng,2005,24:924-929.
42. Vaalburg W, Hendrikse NH, Elsinga PH, et al. P-glycoprotein activity and biological and biological response. Toxicol Appl Pharmacol,2005,207:257-260.
43. Ise T, Shimizu T, Lee EL, et al. Roles of volume-sensitive Cl Channel in cisplatin-induced apoptosis in human epidermoid cancer cells. J Membr Biol, 2005,(3):139-145.
44. Sun D, Lennernas H, Welage LS, et al. Comparison of human duodenum and Caco-2 gene expression profiles for 120000 gene sequences tags and correlation with permeability of 26 drugs. Pharm Res,2002,19:1400-1416.
45. Woo J, Lee J, Kim MS, et al. The effect of aquaporin 5 overexpression on the Ras signaling pathway. Biochem Biophys Res Commun.2008,367(2):291
46. Hiranmoy Bhattacharjee, Barry P Rosen, Rita Mukhopadhyay. Aquaglyceroporins and metalloid transport:Implication in human diseases. Handb Exp Pharmacol, 2009,190:309-325.
47. Jordy Leung, Annie Pang, Wai-Hung Yuen et al. Relationship of expression of aquaglycer 9 with arsenic uptake and sensitivity in leukemia cells. Blood,2007, 109:740-746.
48. Nestor L. Uzcategui, Yao Zhou, Katherine Figarella, et al. Alteration in glycerol and metalloid permeability by a single mutation in the extracellular C-loop of Leishmania major aquaglyceroporin LmAQPl. Mol Microbiol,2008,70(6): 1365-2958.
49. Naranmandura H, Ogra Y, Iwata K. Evidence for toxicity differences between inorganic arsenite and thioarsenicals in human bladder cancer cells. Toxicol Appl Pharmaco,2009,238(2):133-40.