JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2015, Vol. 53 ›› Issue (6): 33-38.doi: 10.6040/j.issn.1671-7554.0.2014.944

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A microarray analysis of bortezomib-resistant gene expression in multiple myeloma

LIU Qiong1, PU Yedi2, DAI Guangxia1, MA Jiale1, YANG Jianxia1, LI Lizhen1, LI Hao1, WANG Luqun1   

  1. 1. Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    2. Department of Hematology, Tianjin First Center Hospital, Tianjin 300192, China
  • Received:2014-12-11 Revised:2015-02-28 Online:2015-06-10 Published:2015-06-10

Abstract: Objective To investigate genes related to bortezomib-resistance phenotype by analyzing different gene expression patterns with cDNA microarray and explore the mechanism of bortezomib-resistant myeloma. Methods Gene expression profiles of KM3/BTZ and KM3 cell lines were compared using Affymetrix U133 plus 2.0 oligonucleotide microarray. Specific differently-expressed genes were chosen for further verification by real-time RT-PCR. Relevant data were analyzed with molecular annotation system MAS3.0 software and compared with documented resistance genes. Results It was found that the KM3/BTZ cell line had 670 differently expressed genes as compared to KM3, of which 32 genes were increased or decreased by more than 10 folds. These 32 genes were involved in the regulation of transcription and signal transduction. Some genes of ZNF and MS4A family and HSPB2 were lowly expressed in KM3, but highly expressed in KM3/BTZ. Except for JUN, 7 genes (CA12, CYP1B1, EPB41L3, HSPB2, MS4A4A, SDPR, PAWR) were further verified using real-time RT-PCR and results were consistent with the microarray. Conclusion Some members of ZNF and MS4A family and another 30 genes whose differential expression is more than 10 folds between KM3 and KM3/BTZ may be related to bortezomib-resistance in multiple myeloma cells. Combination of filteringgenes and detailed analysis of documented resistance genes provides a potential approach to investigate the mechanism of drug resistance in multiple myeloma cells.

Key words: Multiple myeloma, Drug resistance, Bortezomib, cDNA microarray

CLC Number: 

  • R733.3
[1] Mitsiades N, Mitsiades CS, Poulaki V, et al. Molecular sequelae of proteasome inhibitionin human multiple myeloma cells[J]. Proc Natl Acad Sci USA, 2002, 99(22):14374-14379.
[2] Zheng B, Zhou R, Gong Y, et al. Proteasome inhibitor bortezomib overcomes P-gp-mediated multidrug resistance in resistant leukemia cell lines[J]. Biochemical Int J Lab Hematol, 2012, 34(3):237-247.
[3] 蒲业迪, 李丽珍, 马道新, 等. 硼替佐米耐药多发性骨髓瘤细胞株KM3/BTZ的建立[J]. 山东大学学报:医学版, 2013, 51(2):33-36. PU Yedi, LI Lizhen, MA Daoxin, et al. Establishment of a bortezomib-resistant cell line KM3/BTZ of human multiple myeloma[J]. Journal of Shandong University:Health Sciences, 2013, 51(2):33-36.
[4] 李荣, 侯建. 新药时代造血干细胞移植治疗多发性骨髓瘤若干问题探讨[J]. 中国实用内科杂志, 2014, 34(2):115-117. LI Rong, HOU Jian. Several issues concerning hematopoietic stem cell transplantation in treatment of multiple myeloma in the new drugarea[J]. Chinese Journal of Practical Internal Medicine, 2014, 34(2):115-117.
[5] Palumbo A, Ambrosini MT, Benevolo G, et al. Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma[J]. Blood, 2007, 109(7):2767-2772.
[6] Berenson JR, Yang HH, Sadler K, et al. Phase I/II trial assessing bortezomib and melphalan combination therapy for the treatment of patients with relapsed or refractory multiple myeloma[J]. J Clin Oncol, 2006, 24(6):937-944.
[7] Richardsom PG, Xie W, Jagannath S, et al. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma[J]. Blood, 2014, 123(10):1461-1469.
[8] Chauhan D, Li G, Shringarpure R, et al. Blockade of Hsp27 overcomes bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells[J]. Cancer Res, 2003, 63(69):6174-6177.
[9] Oerlemans R, Franke NE, Assaraf YG, et al. Molecular basis of bortezomib resistance:proteasome subunit beta5(PSMB5) gene mutation and overexpression of PSMB5 protein[J]. Blood, 2008, 112(6):2489-2499.
[10] Carrasco DR, Sukhdeo K, Protopopova M, et al. The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis[J]. Cancer Cell, 2007, 411(4):349-360.
[11] Teru Hideshima, Klaus Podar, Dharminder Chauhan, et al. p38 MAPK inhibition enhances PS-341 (bortezomib)-induced cytotoxicity against multiple myeloma cells[J]. Oncogene, 2004, 23(54):8766-8776.
[12] Wang BD, Kline CL, Pastor DM, et al. Prostate apoptosis response protein 4 sensitizes human colon cancer cells to chemotherapeutic 5-FU through mediation of an NF kappaB and microRNA network[J]. Mol Cancer, 2010, 430(9):1186-1476.
[13] Takagi Y, Nozaki K, Sugino T, et al. Phosphorylation of c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase after transient forebrain ischemia in mice[J]. Neurosci Lett, 2000, 294(2):117-120.
[14] Shringarpure R, Catley L, Bhole D, et al.Gene expression analysis of B-lymphoma cells resistant and sensitive to bortezomib[J]. Br J Haematol, 2006, 134(2):145-156.
[15] Hoovers J, Mannens M, John R, et al. High-resolution localization of 69 potential human zinc finger protein genes:A number are clustered[J]. Genomics, 1992, 12(2):254-263.
[16] Huebner K, Druck T, Croce C, et al. Twenty-seven nonoverlapping zinc finger cDNAs from human T cells map to nine different chromosomes with apparent clustering[J]. Am J Hum Genet, 1991, 48(4):726-740.
[17] Duan Z, Choy E, Harmon D, et al. ZNF93 increases resistance to ET-743 (Trabectedin; Yondelis) and PM00104 (Zalypsis) in human cancer cell lines[J]. PLoS One, 2009, 6(9):728-732.
[18] Liang Y, Buckley TR, Tu L, et al. Structural organization of the human MS4A gene cluster on Chromosome 11q12[J]. Immunogenetics, 2001, 53(5):357-368.
[19] Liang Y, Tedder TF. Identification of a CD20-, FcepsilonRIbeta-, and HTm4 related gene family:sixteen new MS4A family members expressed in human and mouse[J]. Genomics, 2001, 72(2):119-127.
[20] Kutok JL, Yang X, Folkerth R, et al. Characterization of the expression of HTm4 (MS4A3), a cell cycle regulator, in human peripheral blood cells and normal and malignant tissues[J]. J Cell Mol Med, 2011, 15(1):86-93.
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