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Journal of Chinese Integrative Medicine ›› 2006, Vol. 4 ›› Issue (2): 160-165.doi: 10.3736/jcim20060211

• Original Experimental Research • Previous Articles     Next Articles

Changes of gene expression profile of multiple myeloma cell line RPMI 8226 treated by arsenic trioxide

Meng-chang Wang1, Shan-xi Liu1, Peng-bo Liu2   

  1. 1. Department of Hematology, First Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi Province 710061, China
    2. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30022, USA
  • Online:2006-03-20 Published:2006-03-15


To compare the changes of gene expression profiles of multiple myeloma cell line RPMI 8226 before and after 24-hour intervention of arsenic trioxide.


The responses of the RPMI 8226 cells to arsenic trioxide were determined with cDNA microarray which included 4 096 different human genes.


Of these 4 096 genes, the expressions of 273 genes were altered significantly at mRNA level. The expressions of 121 genes were up-regulated while the expressions of 152 genes were down-regulated.


The effect of arsenic trioxide on RPMI 8226 cells is related to changing the expression levels of a number of genes. ZFYVE16, ALK1 and TXNIP genes may play important roles in apoptosis and differentiation of RPMI 8226 cells.

Key words: Arsenic trioxide, DNA microarray, Multiple myeloma

CLC Number: 

  • R733.3

Table 1

Up-regulated genes in RPMI 8226 cell samples after arsenic trioxide intervention"

Classification Gene number in GeneBank (gene symbol)
Proto-oncogenes and tumor suppressor genes NM_015907 (LAP3) NM_006290 (TNFAIP3)
Ion-channel and transporter genes NM_005827 (SLC35B1)
Cell cycle genes NM_005402 (RALA) NM_031966 (CCNB1) NM_003503 (CDC7)
NM_005496 (SMC4L1)
Stress response protein genes NM_002663 (PLD2)
Cytoskeletal protein genes XM_375851 (KIAA0133) NM_000533 (PLP1) NM_001888 (CRYM)
Apoptosis-related genes NM_003368 (USP1)
DNA synthesis-related genes NM_006479 (RAD51AP1) NM_012415 (RAD54B)
DNA binding-related genes NM_014766 (SCRN1) NM_170751 (CDYL) NM_005966 (NAB1)
NM_003472 (DEK)
Immune-related genes NM_006499 (LGALS8) NM_000014 (A2M) NM_004685 (MTMR6)
NM_001548 (IFIT1)
Signal transduction-related genes NM_005288 (GPR12) NM_004598 (SPOCK) NM_006159 (NELL2)
NM_001709 (BDNF) NM_198794 (MAP4K5) NM_005388 (PDCL)
NM_004730 (ETF1)
Metabolism-related genes NM_000416 (IFNGR1) NM_017887 (FLJ20580) NM_003866 (INPP4B)
NM_006246 (PPP2R5E) NM_000484 (APP) NM_000108 (DLD)
NM_004130 (GYG) NM_003645 (SLC27A2) NM_005857 (ZMPSTE24)
NM_001172 (ARG2) NM_000274(OAT)
Protein synthesis related genes NM_002816 (PSMD12) NM_006558 (KHDRBS3) NM_014498 (GOLPH4)
Development-related genes AK024833 NM_012124 (CHORDC1)
Other genes AK127112 NM_006461 (SPAG5) NM_015941 (ATP6V1H)
NM_178432 (CCRK) NM_198402 (PTPLB) NM_014028 (OSTM1)
NM_017819 (RG9MTD1) NM_012111 (AHSA1) NM_016447 (MPP6)
NM_012262 (HS2ST1) NM_005647 (TBL1X) NM_017632 (CARF)
NM_005863 (NET1) NM_016013 (NDUFAF1) AK023131
NM_007245 (ATXN2L) NM_014791 (MELK) NM_015149 (RGL1)
Unclassified genes NM_002245 (KCNK1) NM_003384 (VRK1) NM_016281 (TAOK3)
NM_007039 (PTPN21) BF740306 NM_005748 (YAF2)
NM_001260 (CDK8) NM_014393 (STAU2) NM_000071 (CBS)
NM_001731 (BTG1) NM_007131 (ZNF75) NM_199040 (NUDT4)
NM_004326 (BCL9) NM_012145 (DTYMK) NM_012322 (LSM5)
NM_002874 (RAD23B) NM_002047 (GARS) NM_005802 (TOPORS)
NM_006136 (CAPZA2) NM_014669 (NUP93) NM_004412 (DNMT2)
NM_014268 (MAPRE2) AL080215 NM_004694 (SLC16A6)
NM_001814 (CTSC) NM_006276 (SFRS7) BM906503
NM_004938 (DAPK1) NM_006391 (IPO7) NM_001357 (DHX9)
NM_005900 (SMAD1) NM_002669 (PLRG1) NM_001957 (EDNRA)
NM_005657 (TP53BP1) NM_015072 (KIAA0998) NM_004456 (EZH2)
NM_002128 (HMGB1) NM_030755 (TXNDC) NM_002037 (FYN)
NM_002806 (PSMC6) NM_001353 (AKR1C1) NM_000771 (CYP2C9)
NM_020739 (CCPG1) AA362161 NM_001423 (EMP1)
NM_004375 (COX11) XM_045290 (LOC151579) NM_001539 (DNAJA1)
NM_018976 (SLC38A2) NM_020474 (GALNT1) NM_015474 (SAMHD1)
NM_005627 (SGK) NM_006195 (PBX3) NM_003266 (TLR4)
NM_006003 (UQCRFS1) XM_375086 (ZBTB1) NM_014733 (ZFYVE16)
NM_002982 (CCL2)

Table 2

Down-regulated genes in RPMI 8226 cell samples after arsenic trioxide intervention"

Classification Gene number in GeneBank (gene symbol)
Proto-oncogenes and tumor suppressor genes NM_006875 (PIM2) NM_005433 (YES1)
Ion-channel and transporter genes NM_000463 (UGT1A1) NM_005817 (M6PRBP1)
Cell cycle genes NM_004356 (CD81) NM_004344 (CETN2) NM_020307 (CCNL1)
Cytoskeletal protein genes NM_006825 (CKAP4) NM_004368 (CNN2) X62167
Apoptosis-related genes NM_016085 (C2orf28)
DNA synthesis-related genes NM_005999 (TSNAX) NM_004650 (PNPLA4)
DNA binding-related genes NM_006298 (ZNF192)
Cell receptor genes NM_001470 (GABBR1) NM_000952 (PTAFR) NM_014053 (FLVCR)
NM_003023 (SH3BP2)
Immune-related genes NM_004661 (CDC23) NM_001823 (CKB)
Signal transduction-related genes NM_000581(GPX1) NM_002900 (RBP3) D84454
NM_001078 (VCAM1) NM_002437 (MPV17) AL117607
NM_001388 (DRG2) NM_033018 (PCTK1) NM_016086 (DUSP24)
NM_003929 (RAB7L1) NM_005107 (ENDOGL1) NM_004995 (MMP14)
NM_005012 (ROR1)
Metabolism-related genes NM_012203 (GRHPR) NM_004419 (DUSP5) BC000747 (EXOSC2)
NM_000294 (PHKG2) NM_002970 (SAT) BC001926 (CKMT1)
NM_000527 (LDLR)
Protein synthesis related genes NM_002192 (INHBA) NM_003450 (ZNF174)
Development-related genes NM_022728 (NEUROD6)
Other genes NM_006472(TXNIP) NM_006108 (SPON1) NM_019058 (DDIT4)
NM_016835 (MAPT) NM_006826 (YWHAQ) NM_019110 (ZNF307)
NM_005165 (ALDOC) AB020644 NM_014042(DKFZP564M082)
NM_015470 (RAB11FIP5) NM_005056 (JARID1A) NM_199188 (LOC113251)
AB011129 NM_016063 (C6orf74) NM_012402 (ARFIP2)
NM_001047 (SRD5A1) NM_005004 (NDUFB8)
Unclassified genes NM_000020 (ACVRL1) NM_015909 (NAG) NM_001775 (p45) (CD38)
CD642056 NM_020185 (DUSP22) NM_000666 (ACY1)
NM_002124 (HLA-DRB1) NM_000228 (LAMB3) AF150249
NM_031469 (SH3BGRL2) NM_000636 (SOD2) AA335318
NM_003447 (ZNF165) XM_168101 (LOC221766) NM_014648(DZIP3)
BG547283 NM_006432 (NPC2) NM_021026 (RFPL1)
BC051746 NM_198040 (PHC2) NM_000820 (GAS60)
NM_012190 (FTHFD) NM_003803 (MYOM1) NM_003315 (DNAJC7)
NM_006087 (TUBB4) NM_002124 (HLA-DRB1) BC037952
NM_002530 (NTRK3) NM_003033 (SIAT4A) NM_001966 (EHHADH)
NM_001185(AZGP1) CD367099 AL833286
BC038431 NM_001915 (CYB561) NM_000985 (RPL17)
NM_000276 (OCRL) NM_005398 (PPP1R3C) NM_002431 (MNAT1)
NM_013449 (BAZ2A) NM_001984 (ESD) NM_004385 (CSPG2)
NM_006931 (SLC2A3) NM_002276 (KRT19) NM_000976 (RPL12)
NM_003973 (RPL14) NM_003487 (TAF15) NM_015173 (TBC1D1)
NM_003879 (CFLAR) NM_006303 (JTV1) NM_016328 (GTF2IRD1)
M90391 NM_000232 (SGCB) NM_014210 (EVI2A)
NM_000990(RPL27A) AA558497 BX096847
NM_003035 (SIL) NM_198336 (INSIG1) NM_005730 (CTDSP2)
NM_002003 (FCN1) AA877719 NM_012423 (RPL13A)
BC036774 NM_018997 (MRPS21) NM_000249 (MLH1)
NM_198893 (ZNF160) NM_003526 (HIST1H2BC) NM_021047 (ZNF253)
NM_005637 (SS18) NM_002074 (GNB1) BX362771
BM930758 BM975105 BC043351 (JRK)
BC034279 XM_378757 (LOC284276) NM_006402 (HBXIP)
NM_001017 (RPS13) NM_002026 (FN1) NM_020856 (ZNF537)
NM_005470 (ABI1) NM_017841 (FLJ20487) NM_006280 (SSR4)
NM_001032 (RPS29) NM_000970 (RPL6) NM_005629 (SLC6A8)
NM_139321 (ATRN) NM_052874 (STX1B2) AK022805
NM_005184 (CALM3) NM_015033 (FNBP1)

Figure 1

Superposition maps of Cy5- and Cy3-labeled RPMI 8226 cell samples treated with and without arsenic trioxide On one spot, if Cy3 signal was much stronger than Cy5 signal, it showed green (i.e. down-regulation); if Cy5 signal was much stronger than Cy3 signal, it showed red (i.e. up-regulation); if the intensities of Cy3 and Cy5 signals were similar, it showed yellow."

Figure 2

Scatter diagram of Cy5/Cy3 ratios in RPMI 8226 cell samples treated with and without arsenic trioxideX-axis and Y-axis represented the fluorescence intensities of Cy3 and Cy5 respectively. Each point in the scatter diagram represented the hybridization signal of corresponding gene in DNA microarray. The red point meant that the Cy5/Cy3 ratio was within the range of 0.5 to 2.0 (with no significant difference in gene expression). The yellow point meant that the Cy5/Cy3 ratio was beyond the range of 0.5 to 2.0 (with significant difference in gene expression)."

[1] Dalton WS . Targeting the mitochondria: an exciting new approach to myeloma therapy[J]. Clin Cancer Res, 2002,8(12):3643-3645
[2] Amadori S, Fenaux P, Ludwig H , et al. Use of arsenic trioxide in haematological malignancies: insight into the clinical development of a novel agent[J]. Curr Med Res Opin, 2005,21(3):403-411
[3] Matsuda S, Rouault J, Magaud J , et al. In search of a function for the TIS21/PC3/BTG1/TOB family[J]. FEBS Lett, 2001,497(2-3):67-72
doi: 10.1016/S0014-5793(01)02436-X pmid: 11377414
[4] Prevot D, Voeltzel T, Birot AM , et al. The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation[J]. J Biol Chem, 2000,275(1):147-153
[5] Lin WJ, Gary JD, Yang MC , et al. The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase[J]. J Biol Chem, 1996,271(25):15034-15044
[6] Iwai K, Hirata K, Ishida T , et al. An anti-proliferative gene BTG1 regulates angiogenesis in vitro[J]. Biochem Biophys Res Commun, 2004,316(3):628-635
doi: 10.1016/j.bbrc.2004.02.095 pmid: 15033446
[7] Seet LF, Hong W . Endofin, an endosomal FYVE domain protein[J]. J Biol Chem, 2001,276(45):42445-42454
doi: 10.1074/jbc.M105917200 pmid: 11546807
[8] Seet LF, Liu N, Hanson BJ , et al. Endofin recruits TOM1 to endoscomes[J]. J Biol Chem, 2004,279(6):4670-4679
doi: 10.1074/jbc.M311228200 pmid: 14613930
[9] Seet LF, Hong W . Endofin recruits clathrin to early endosomes via TOM1[J]. J Cell Sci, 2005,118(Pt 3):575-587
doi: 10.1242/jcs.01628 pmid: 15657082
[10] Iwabuchi K, Li B, Massa HF , et al. Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53BP1 and 53BP2[J]. J Biol Chem, 1998,273(40):26061-26068
[11] Goumans MJ, Valdimarsdottir G, Itoh S , et al. Activin receptor-like kinase(ALK)1 is an antagonistic mediator of lateral TGFbeta/ALK5 signaling[J]. Mol Cell, 2003,12(4):817-828
[12] Sugawara K, Sugawara I, Sukegawa J , et al. Distribution of C-yes-1 gene product in various cells and tissues[J]. Br J Cancer, 1991,63(4):508-513
doi: 10.1038/bjc.1991.121 pmid: 18507
[13] Hui TY, Sheth SS, Diffley JM , et al. Mice lacking thioredoxin-interacting protein provide evidence linking cellular redox state to appropriate response to nutritional signals[J]. J Biol Chem, 2004,279(23):24387-24393
[14] Jia P, Chen G, Huang X , et al. Arsenic trioxide induces multiple myeloma cell apoptosis via disruption of mitochondrial transmembrane potentials and activation of caspase-3[J]. Chin Med J (Engl), 2001,114(1):19-24
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