DADS对DJ-1核定位高表达人白血病HL-60细胞的影响（英文）
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摘要
最近研究表明,DJ-1在许多肿瘤中过表达,而且DJ-1的核表达与肿瘤的生物学行为有关.本文主要研究二烯丙基二硫(DADS)对DJ-1核定位高表达人白血病HL-60细胞生物行为学的影响,阐明DJ-1在细胞核内的功能,为临床诊断及治疗过程提供一个潜在的治疗靶点.通过基因转染技术建立核内高表达HL-60细胞株(DJ-1/HL-60),利用软琼脂集落形成实验、 MTT法、间接免疫荧光细胞化学实验、硝基蓝四氮唑(NBT)还原比色实验评估HL-60细胞的增殖与分化,DJ-1核定位过表达促进HL-60细胞的增殖并抑制其分化. Transwell迁移侵袭小室实验表明DJ-1核定位过表达可以促进HL-60的迁移和侵袭能力. Western blot结果表明DADS具有抑制HL-60细胞中核内DJ-1蛋白表达的能力.说明DJ-1核定位高表达具有促进HL-60细胞增殖和迁移侵袭及抑制HL-60细胞分化的作用,DADS可以诱导DJ-1核定位高表达HL-60细胞分化及抑制迁移侵袭, DJ-1核定位高表达可减弱DADS抑制HL-60细胞增殖的作用.
Recent studies have revealed that DJ-1 is overexpressed in multiple forms of human tumors, and nuclear overexpression of DJ-1 is correlated with the biological behavior of tumor. The purpose of the present study was to test for possible DADS effects on Human Leukemia HL-60 cells which DJ-1 is overexpressed, and to clarify the function of DJ-1 in the nucleus.Gene transfection technology was used to establish stable HL-60 cell lines with nuclear overexpression of DJ-1(DJ-1/HL-60). Soft agar colony formation, MTT, NBT and indirect immunofluorescence were used to evaluate the proliferation, differentiation,migration and invasion of HL-60 cells. The nuclear overexpression of DJ-1 protein may promote the proliferation and weaken the differentiation of HL-60 cells. Transwell migration and invasion assays showed that the nuclear localization and overexpression of DJ-1 can promote the migration and invasion capability of HL-60. Western blot analysis revealed that the expression of DJ-1 was inhibited in HL-60 cells with nuclear overexpression of DJ-1 after treatment with DADS. These results defined the impacts of DJ-1 on biological behavior of the Human Leukemia HL-60 cells by DADS, the proliferation, migration and invasion were inhibited and the differentiation was induced in HL-60 cells with nuclear overexpression of DJ-1, after treatment with DADS.
Recent studies have revealed that DJ-1 is overexpressed in multiple forms of human tumors, and nuclear overexpression of DJ-1 is correlated with the biological behavior of tumor. The purpose of the present study was to test for possible DADS effects on Human Leukemia HL-60 cells which DJ-1 is overexpressed, and to clarify the function of DJ-1 in the nucleus.Gene transfection technology was used to establish stable HL-60 cell lines with nuclear overexpression of DJ-1(DJ-1/HL-60). Soft agar colony formation, MTT, NBT and indirect immunofluorescence were used to evaluate the proliferation, differentiation,migration and invasion of HL-60 cells. The nuclear overexpression of DJ-1 protein may promote the proliferation and weaken the differentiation of HL-60 cells. Transwell migration and invasion assays showed that the nuclear localization and overexpression of DJ-1 can promote the migration and invasion capability of HL-60. Western blot analysis revealed that the expression of DJ-1 was inhibited in HL-60 cells with nuclear overexpression of DJ-1 after treatment with DADS. These results defined the impacts of DJ-1 on biological behavior of the Human Leukemia HL-60 cells by DADS, the proliferation, migration and invasion were inhibited and the differentiation was induced in HL-60 cells with nuclear overexpression of DJ-1, after treatment with DADS.
引文
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[15]Liu H,Wang M,Li M,et al.Expression and role of DJ-1 in leukemia.Biochem Biophys Res Commun,2008,375(3):477-483
[16]Nagakubo D,Taira T,Kitaura H,et al.DJ-1,a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras.Biochem Biophys Res Commun,1997,231(2):509-513
[17]Bonifati V,Rizzu P,van Baren M J,et al.Mutations in the DJ-1gene associated with autosomal recessive early-onset parkinsonism.Science,2003,299(5604):256-259
[18]Canet-Aviles R M,Wilson M A,Miller D W,et al.The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization.Proc Natl Acad Sci U S A,2004,101(24):9103-9108
[19]Li H M,Niki T,Taira T,et al.Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress.Free Radic Res,2005,39(10):1091-1099
[20]Junn E,Taniguchi H,Jeong B S,et al.Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death.Proc Natl Acad Sci U S A,2005,102(27):9691-9696
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[23]Yi L,Ji X X,Tan H,et al.Involvement of Mcl1 in diallyl disulfideinduced G2/M cell cycle arrest in HL-60 cells.Oncol Rep,2012,27(6):1911-1917
[24]Tan H,Ling H,He J,et al.Inhibition of ERK and activation of p38are involved in diallyl disulfide induced apoptosis of leukemia HL-60 cells.Arch Pharm Res,2008,31(6):786-793
[25]Poschmann G,Lendzian A,Uszkoreit J,et al.A combination of two electrophoretical approaches for detailed proteome-based characterization of SCLC subtypes.Arch Physiol Biochem,2013,119(3):114-125
[26]Lu L,Sun X,Liu Y,et al.DJ-1 upregulates tyrosine hydroxylase gene expression by activating its transcriptional factor Nurr1 via the ERK1/2 pathway.Int J Biochem Cell Biol,2012,44(1):65-71
[27]Kato I,Maita H,Takahashi-Niki K,et al.Oxidized DJ-1 inhibits p53 by sequestering p53 from promoters in a DNA-binding affinity-dependent manner.Mol Cell Biol,2013,33(2):340-359
[28]Yang X,Li L,Liang J,et al.Histone acetyltransferase 1 promotes homologous recombination in DNA repair by facilitating histone turnover.J Biol Chem,2013,288(25):18271-18282
[29]Lee H,Choi S K,Ro J Y.Overexpression of DJ-1 and HSP90alpha,and loss of PTEN associated with invasive urothelial carcinoma of urinary bladder:possible prognostic markers.Oncol Lett,2012,3(3):507-512
[30]Arnouk H,Merkley M A,Podolsky R H,et al.Characterization of molecular markers indicative of cervical cancer progression.Proteomics Clin Appl,2009,3(5):516-527
[31]Gopinath R S,Ambagala A P,Ambagala T C,et al.Molecular cloning and characterization of c DNA encoding CD11b of cattle.Vet Immunol Immunopathol,2006,110(3-4):349-355
[32]Du Mont A L,Yoong P,Day C J,et al.Staphylococcus aureus Luk AB cytotoxin kills human neutrophils by targeting the CD11b subunit of the integrin Mac-1.Proc Natl Acad Sci U S A,2013,110(26):10794-10799
[33]董婷,蒋雅先,李正发,等.急性早幼粒细胞白血病的细胞表面免疫分子的检测和分析.2017,33(5):664-667Dong T,Jiang Y X,Li Z F,et al.Chinese Journal of Cellular and Molecular Immunology,2017,33(5):664-667
[34]He X,Zheng Z,Li J,et al.DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/u PA.Carcinogenesis,2012,33(3):555-562
[35]Tillman J E,Yuan J,Gu G,et al.DJ-1 binds androgen receptor directly and mediates its activity in hormonally treated prostate cancer cells.Cancer Res,2007,67(10):4630-4637
[2]Yi L,Su Q.Molecular mechanisms for the anti-cancer effects of diallyl disulfide.Food Chem Toxicol,2013,57:362-370
[3]Ling H,He J,Tan H,et al.Identification of potential targets for differentiation in human leukemia cells induced by diallyl disulfide.Int J Oncol,2017,50(2):697-707
[4]Zhao J,Huang W G,He J,et al.Diallyl disulfide suppresses growth of HL-60 cell through increasing histone acetylation and p21WAF1 expression in vivo and in vitro.Acta Pharmacol Sin,2006,27(11):1459-1466
[5]Jung H J,Kim S,Kim Y J,et al.Dissection of the dimerization modes in the DJ-1 superfamily.Mol Cells,2012,33(2):163-171
[6]Kawate T,Tsuchiya B,Iwaya K.Expression of DJ-1 in cancer cells:its correlation with clinical significance.Adv Exp Med Biol,2017,1037:45-59
[7]Li Y,Cui J,Zhang C H,et al.High-expression of DJ-1 and loss of PTEN associated with tumor metastasis and correlated with poor prognosis of gastric carcinoma.Int J Med Sci,2013,10(12):1689-1697
[8]Osman W M,Abd E A R,Abou G H.DJ-1 and androgen receptor immunohistochemical expression in prostatic carcinoma:a possible role in carcinogenesis.J Egypt Natl Canc Inst,2013,25(4):223-230
[9]Pei X J,Wu T T,Li B,et al.Increased expression of macrophage migration inhibitory factor and DJ-1 contribute to cell invasion and metastasis of nasopharyngeal carcinoma.Int J Med Sci,2014,11(1):106-115
[10]Zhu H,Liao S D,Shi J J,et al.DJ-1 mediates the resistance of cancer cells to dihydroartemisinin through reactive oxygen species removal.Free Radic Biol Med,2014,71:121-132
[11]Kawase H,Fujii K,Miyamoto M,et al.Differential LC-MS-based proteomics of surgical human cholangiocarcinoma tissues.JProteome Res,2009,8(8):4092-4103
[12]Kawate T,Iwaya K,Koshikawa K,et al.High levels of DJ-1protein and isoelectric point 6.3 isoform in sera of breast cancer patients.Cancer Sci,2015,106(7):938-943
[13]Zhang H Y,Wang H Q,Liu H M,et al.Regulation of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by DJ-1 in thyroid cancer cells.Endocr Relat Cancer,2008,15(2):535-544
[14]Bai J,Guo C,Sun W,et al.DJ-1 may contribute to metastasis of non-small cell lung cancer.Mol Biol Rep,2012,39(3):2697-2703
[15]Liu H,Wang M,Li M,et al.Expression and role of DJ-1 in leukemia.Biochem Biophys Res Commun,2008,375(3):477-483
[16]Nagakubo D,Taira T,Kitaura H,et al.DJ-1,a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras.Biochem Biophys Res Commun,1997,231(2):509-513
[17]Bonifati V,Rizzu P,van Baren M J,et al.Mutations in the DJ-1gene associated with autosomal recessive early-onset parkinsonism.Science,2003,299(5604):256-259
[18]Canet-Aviles R M,Wilson M A,Miller D W,et al.The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization.Proc Natl Acad Sci U S A,2004,101(24):9103-9108
[19]Li H M,Niki T,Taira T,et al.Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress.Free Radic Res,2005,39(10):1091-1099
[20]Junn E,Taniguchi H,Jeong B S,et al.Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death.Proc Natl Acad Sci U S A,2005,102(27):9691-9696
[21]Xu J,Zhong N,Wang H,et al.The Parkinson's disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis.Hum Mol Genet,2005,14(9):1231-1241
[22]Yuen H F,Chan Y P,Law S,et al.DJ-1 could predict worse prognosis in esophageal squamous cell carcinoma.Cancer Epidemiol Biomarkers Prev,2008,17(12):3593-3602
[23]Yi L,Ji X X,Tan H,et al.Involvement of Mcl1 in diallyl disulfideinduced G2/M cell cycle arrest in HL-60 cells.Oncol Rep,2012,27(6):1911-1917
[24]Tan H,Ling H,He J,et al.Inhibition of ERK and activation of p38are involved in diallyl disulfide induced apoptosis of leukemia HL-60 cells.Arch Pharm Res,2008,31(6):786-793
[25]Poschmann G,Lendzian A,Uszkoreit J,et al.A combination of two electrophoretical approaches for detailed proteome-based characterization of SCLC subtypes.Arch Physiol Biochem,2013,119(3):114-125
[26]Lu L,Sun X,Liu Y,et al.DJ-1 upregulates tyrosine hydroxylase gene expression by activating its transcriptional factor Nurr1 via the ERK1/2 pathway.Int J Biochem Cell Biol,2012,44(1):65-71
[27]Kato I,Maita H,Takahashi-Niki K,et al.Oxidized DJ-1 inhibits p53 by sequestering p53 from promoters in a DNA-binding affinity-dependent manner.Mol Cell Biol,2013,33(2):340-359
[28]Yang X,Li L,Liang J,et al.Histone acetyltransferase 1 promotes homologous recombination in DNA repair by facilitating histone turnover.J Biol Chem,2013,288(25):18271-18282
[29]Lee H,Choi S K,Ro J Y.Overexpression of DJ-1 and HSP90alpha,and loss of PTEN associated with invasive urothelial carcinoma of urinary bladder:possible prognostic markers.Oncol Lett,2012,3(3):507-512
[30]Arnouk H,Merkley M A,Podolsky R H,et al.Characterization of molecular markers indicative of cervical cancer progression.Proteomics Clin Appl,2009,3(5):516-527
[31]Gopinath R S,Ambagala A P,Ambagala T C,et al.Molecular cloning and characterization of c DNA encoding CD11b of cattle.Vet Immunol Immunopathol,2006,110(3-4):349-355
[32]Du Mont A L,Yoong P,Day C J,et al.Staphylococcus aureus Luk AB cytotoxin kills human neutrophils by targeting the CD11b subunit of the integrin Mac-1.Proc Natl Acad Sci U S A,2013,110(26):10794-10799
[33]董婷,蒋雅先,李正发,等.急性早幼粒细胞白血病的细胞表面免疫分子的检测和分析.2017,33(5):664-667Dong T,Jiang Y X,Li Z F,et al.Chinese Journal of Cellular and Molecular Immunology,2017,33(5):664-667
[34]He X,Zheng Z,Li J,et al.DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/u PA.Carcinogenesis,2012,33(3):555-562
[35]Tillman J E,Yuan J,Gu G,et al.DJ-1 binds androgen receptor directly and mediates its activity in hormonally treated prostate cancer cells.Cancer Res,2007,67(10):4630-4637