Browse > Article
http://dx.doi.org/10.7314/APJCP.2014.15.4.1823

HIF-1α and GLUT1 Gene Expression is Associated with Chemoresistance of Acute Myeloid Leukemia  

Song, Kui (Department of Hematology, Nanfang Hospital of Southern Medical University)
Li, Min (Department of Pharmacy, The First Affiliated Hospital of Jishou University)
Xu, Xiao-Jun (Department of Hematology, Nanfang Hospital of Southern Medical University)
Xuan, Li (Department of Hematology, Nanfang Hospital of Southern Medical University)
Huang, Gui-Nian (Department of Hematology, Zhongshan City People's Hospital)
Song, Xiao-Ling (Department of Hematology, Nanfang Hospital of Southern Medical University)
Liu, Qi-Fa (Department of Hematology, Nanfang Hospital of Southern Medical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.4, 2014 , pp. 1823-1829 More about this Journal
Abstract
Aims: Much evidence suggests that increased glucose metabolism in tumor cells might contribute to the development of acquired chemoresistance. However, the molecular mechanisms are not fully clear. Therefore, we investigated a possible correlation of mRNA expression of HIF-$1{\alpha}$ and GLUT1 with chemoresistance in acute myeloid leukemia (AML). Methods: Bone marrow samples were obtained from newly diagnosed and relapsed AML (M3 exclusion) cases. RNA interference with short hairpin RNA (shRNA) was used to stably silence GLUT1 or HIF-$1{\alpha}$ gene expression in an AML cell line and HIF-$1{\alpha}$ and GLUT1 mRNA expression was measured by real-time quantitative polymerase chain reaction assay (qPCR). Results: High levels of HIF-$1{\alpha}$ and GLUT1 were associated with poor responsiveness to chemotherapy in AML. Down-regulation of the expression of GLUT1 by RNA interference obviously sensitized drug-resistant HL-60/ADR cells to adriamycin (ADR) in vitro, comparable with RNA interference for the HIF-$1{\alpha}$ gene. Conclusions: Our data revealed that over-expression of HIF-$1{\alpha}$ and GLUT1 might play a role in the chemoresistance of AML. GLUT1 might be a potential target to reverse such drug resistance.
Keywords
GLUT1; HIF-$1{\alpha}$; glucose metabolism; chemoresistance;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Huang XD, Wang ZF, Dai LM, et al (2012). Microarray analysis of the hypoxia-induced gene expression profile in malignant C6 glioma cells. Asian Pac J Cancer Prev, 13, 4793-9.   DOI   ScienceOn
2 Hao J, Song X, Song B, et al (2008). Effects of lentivirusmediated HIF-1alpha knockdown on hypoxia-related cisplatin resistance and their dependence on p53 status in fibrosarcoma cells. Cancer Gene Ther, 15, 449-55.   DOI   ScienceOn
3 Herst PM, Howman RA, Neeson PJ, et al (2011). The level of glycolytic metabolism in acute myeloid leukemia blasts at diagnosis is prognostic for clinical outcome. J Leukoc Biol, 89, 51-5.   DOI   ScienceOn
4 Hu Y, Kirito K, Yoshida K, et al (2009). Inhibition of hypoxiainducible factor-1 function enhances the sensitivity of multiple myeloma cells to melphalan. Mol Cancer Ther, 8, 2329-38.
5 Hulleman E, Kazemier KM, Holleman A, et al (2009). Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells. Blood, 113, 2014-21.   DOI   ScienceOn
6 Kluza J, Jendoubi M, Ballot C, et al (2011). Exploiting mitochondrial dysfunction for effective elimination of imatinib-resistant leukemic cells. PLoS One, 6, e21924.   DOI
7 Kominsky DJ, Klawitter J, Brown JL, et al (2009). Abnormalities in glucose uptake and metabolism in imatinib-resistant human BCR-ABL-positive cells. Clin Cancer Res, 15, 3442-50.   DOI   ScienceOn
8 Lu CW, Lin SC, Chen KF, et al (2008). Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance. J Biol Chem, 283, 28106-14.   DOI   ScienceOn
9 Manel N, Battini JL, Sitbon M (2005). Human T cell leukemia virus envelope binding and virus entry are mediated by distinct domains of the glucose transporter GLUT1. J Biol Chem, 280, 29025-9.   DOI   ScienceOn
10 Takubo K, Goda N, Yamada W, et al (2010). Regulation of the HIF-1a level is essential for hematopoietic stem cells. Cell Stem Cell, 7, 391-402.   DOI   ScienceOn
11 Tamada M, Nagano O, Tateyama S, et al (2012). Modulation of glucose metabolism by CD44 contributes to antioxidant status and drug resistance in cancer cells. Cancer Res, 72, 1438-48.   DOI   ScienceOn
12 Wynn ML, Merajver SD, Schnell S (2012). Unraveling the complex regulatory relationships between metabolism and signal transduction in cancer. Adv Exp Med Biol, 736, 179-89.   DOI
13 Zhou Y, Tozzi F, Chen J, et al (2012). Intracellular ATP levels are a pivotal determinant of chemoresistance in colon cancer cells. Cancer Res, 72, 304-14.   DOI   ScienceOn
14 Zhou Y, Tozzi F, Chen J, et al (2012). Intracellular ATP levels are a pivotal determinant of chemoresistance in colon cancer cells. Cancer Res, 72, 304-14.   DOI   ScienceOn
15 Papageorgis P, Cheng K, Ozturk S, et al (2011). Smad4 inactivation promotes malignancy and drug resistance of colon cancer. Cancer Res, 71, 998-1008.   DOI   ScienceOn
16 Chinese Chemotherapy Symposium of Leukemia (1988). The chemotherapy response criteria of acute leukemia. Chin J Hematol, 9, 183-4.
17 Chen EI (2012). Mitochondrial dysfunction and cancer metastasis. J Bioenerg Biomembr, 44, 619-22.   DOI   ScienceOn
18 Buentke E, Nordstrom A, Lin H, et al (2011). Glucocorticoidinduced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells. Blood Cancer J, 1, e31.   DOI   ScienceOn
19 Chen CY, Jia JH, Zhang MX, et al (2005). Proteomic analysis on multi-drug resistant cells HL-60/DOX of acute myeloblastic leukemia. Chin J Physiol, 48, 115-20.
20 Chung FY, Huang MY, Yeh CS, et al (2009). GLUT1 gene is a potential hypoxic marker in colorectal cancer patients. BMC Cancer, 9, 241.   DOI   ScienceOn
21 Comito G, Calvani M, Giannoni E, et al (2011). HIF-1$\alpha$ stabilization by mitochondrial ROS promotes Met-dependent invasive growth and vasculogenic mimicry in melanoma cells. Free Radic Biol Med, 51, 893-904.   DOI   ScienceOn
22 Deeb G, Vaughan MM, McInnis I, et al (2011). Hypoxiainducible factor-1$\alpha$ protein expression is associated with poor survival in normal karyotype adult acute myeloid leukemia. Leuk Res, 35, 579-84.   DOI   ScienceOn
23 Deeb G, Vaughan MM, McInnis I, et al (2011). Hypoxiainducible factor-1$\alpha$ protein expression is associated with poor survival in normal karyotype adult acute myeloid leukemia. Leuk Res, 35, 579-84.   DOI   ScienceOn
24 Amann T, Maegdefrau U, Hartmann A, et al (2009). GLUT1 expression is increased in hepatocellular carcinoma and promotes tumorigenesis. Am J Pathol, 174, 1544-52.   DOI   ScienceOn
25 Pelicano H, Martin DS, Xu RH, et al (2006). Glycolysis inhibition for anticancer treatment. Oncogene, 25, 4633-46.   DOI   ScienceOn
26 Bayley JP, Devilee P (2012). The Warburg effect in 2012. Curr Opin Oncol, 24, 62-7.   DOI   ScienceOn
27 Matsunaga T, Imataki O, Torii E, et al (2012). Elevated HIF- 1$\alpha$ expression of acute myelogenous leukemia stem cells in the endosteal hypoxic zone may be a cause of minimal residual disease in bone marrow after chemotherapy. Leuk Res, 36, e122-4.   DOI   ScienceOn
28 Moreno-Sanchez R, Rodriguez-Enriquez S, Marin-Hernandez A, et al (2007). Energy metabolism in tumor cells. FEBS J, 274, 1393-418.   DOI   ScienceOn
29 Nakajima EC, Van Houten B (2013). Metabolic symbiosis in cancer: refocusing the Warburg lens. Mol Carcinog, 52, 329-37.   DOI   ScienceOn
30 Patiar S, Harris AL (2006). Role of hypoxia-inducible factor- 1alpha as a cancer therapy target. Endocr Relat Cancer, 13, S61-75.   DOI   ScienceOn
31 Robey IF, Lien AD, Welsh SJ, et al (2005). Hypoxia-inducible factor-1alpha and the glycolytic phenotype in tumors. Neoplasia, 7, 324-30.   DOI
32 Saigusa S, Toiyama Y, Tanaka K, et al (2012). Prognostic significance of glucose transporter-1 (GLUT1) gene expression in rectal cancer after preoperative chemoradiotherapy. Surg Today, 42, 460-9.   DOI   ScienceOn
33 Song X, Liu X, Chi W, et al (2006). Hypoxia-induced resistance to cisplatin and doxorubicin in non-small cell lung cancer is inhibited by silencing of HIF-1alpha gene. Cancer Chemother Pharmacol, 58, 776-84.   DOI   ScienceOn
34 Suh DH, Kim MK, No JH, et al (2011). Metabolic approaches to overcoming chemoresistance in ovarian cancer. Ann N Y Acad Sci, 1229, 53-60.   DOI   ScienceOn
35 Amann T, Hellerbrand C (2009). GLUT1 as a therapeutic target in hepatocellular carcinoma. Expert Opin Ther Targets, 13, 1411-27.   DOI   ScienceOn
36 Cao X, Fang L, Gibbs S, et al (2007). Glucose uptake inhibitor sensitizes cancer cells to daunorubicin and overcomes drug resistance in hypoxia. Cancer Chemother Pharmacol, 59, 495-505.   DOI