β3-乙酰氨基葡萄糖基转移酶对白血病细胞分化的影响及其调控机制
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摘要
已有大量的文献报道:当细胞恶变或分化时,细胞糖复合物上的糖链结构常发生变化,而这种变化来源于某些合成该糖链的相应的糖基转移酶表达的改变。β1,3-N-乙酰氨基葡萄糖转移酶(β3GnTs)家族参于合成其产物中的β1,3-乙酰氨基葡萄糖连接键,其中β3GnT-2, -4, -8亚型合成糖蛋白上N-或O-连接型糖链中的多聚乙酰氨基乳糖结构。本研究探讨这三种酶的表达和四株白血病细胞分化间的关系,以及转录因子Ets-1对β3GnT-2, -4, -8表达的调控。
     本论文分为三个部分:
     一、β3GnT-2, -4, -8和人急性早幼粒白血病细胞株HL60及NB4分化的关系
     目的:研究糖基转移酶β3GnT-2, -4, -8表达变化和人急性早幼粒白血病细胞株HL60及NB4分化的关系。
     方法:RT-PCR检测β3GnT-2, -4, -8在六种不同白血病细胞株中的表达情况。其次,使用ATRA处理HL60和NB4两种人急性早幼粒白血病细胞株,使其向粒细胞方向分化;或用TPA(PMA)处理两种细胞株,使其向单核细胞方向分化。用实时定量PCR(Real-time PCR)检测β3GnT-2, -4, -8的mRNA诱导分化前后在两个细胞株中的表达变化,并结合细胞形态学观察鉴定ATRA、TPA处理前后两个细胞株的形态变化。
     结果:β3GnT-2在白血病细胞株SHI-1,THP-1,K562,HL60,U937,NB4中都有不同程度的表达。β3GnT-4仅在NB4细胞中表达;而β3GnT-8则相反,在NB4细胞中不表达,而在其它5株细胞中有不同程度的表达。在10-7mol/L ATRA或10ng/ml TPA作用2h或3d后,不管HL60和NB4细胞株向何方向分化,其β3GnT-2, -4, -8的mRNA表达与不加分化诱导剂的对照组相比均见不同程度的升高。其中以β3GnT-4的改变最为显著,且有时间依赖性变化。β3GnT-8和β3GnT-2的上升幅度大致相近。ATRA使HL60和NB4细胞向粒细胞分化时,βGnTs的上调较TPA使两种细胞向单核细胞分化时明显;而HL60细胞的β3GnTs对两个分化诱导剂的上调作用较NB4细胞更为敏感。
     结论:早幼粒白血病细胞HL60和NB4在ATRA或TPA诱导向不同方向分化时,可见β3GnT-2, -4, -8的表达有不同程度的增加。ATRA的作用强于TPA;而HL60细胞对分化诱导剂的敏感性强于NB4细胞。
     二、β3GnT-2, -4, -8和人单核白血病细胞株SHI-1及THP-1分化的关系
     目的:研究糖基转移酶β3GnT-2, -4, -8表达变化和人单核白血病细胞株SHI-1及THP-1分化的关系。
     方法:在第一部分研究的基础上,改用人单核白血病细胞株SHI-1及THP-1为研究对象,用实时定量PCR(Real-time PCR)继续检测β3GnT-2, -4, -8的mRNA在ATRA、TPA处理前后两个细胞株中的表达变化,并结合细胞形态学观察鉴定。
     结果:SHI-1细胞在10-7mol/L ATRA作用2h后,β3GnT-2的mRNA表达即被下调,但3天后回复;而10ng/ml TPA作用2h或3d后,β3GnT-2均上调,第三天更甚。β3GnT-4在TPA处理SHI-1细胞3d后,才见上调,其升高程度与β3GnT-2相仿。β3GnT-8在ATRA或TPA处理3d后才见轻度上调。THP-1细胞对ATRA、TPA均不敏感,其β3GnT-2, -4, -8的表达未见明显改变。与细胞形态学变化一致。
     结论:人单核白血病细胞株对ATRA及TPA的反应均不如人急性早幼粒白血病细胞株敏感,其β3GnT-2, -4, -8的mRNA表达变化不明显。尤其是THP-1细胞对本文所用浓度的ATRA及TPA都没有反应,与细胞形态学不改变相一致。
     三、转录因子Ets-1对β3GnT-2, -4, -8表达的调控研究
     目的:探讨白血病细胞诱导分化过程中Ets-1的表达及其对糖基转移酶对β3GnT-2, -4, -8的转录调控。
     方法:采用Real-time PCR检测HL60、NB4、SHI和THP-1四种白血病细胞中转录因子Ets-1的mRNA在ATRA或TPA处理后的表达变化,并进一步采用染色质免疫沉淀(ChIP)结合凝胶迁移实验(EMSA)检测分析研究前三种细胞中Ets-1和β3GnT基因DNA的结合以及Ets-1对β3GnT的转录调控。
     结果:在ATRA或TPA诱导分化下,HL60细胞中Ets-1 mRNA的表达均有不同程度的升高,且ATRA的作用似乎强于TPA。相反,NB4细胞和SHI-1细胞在ATRA或TPA作用后,总体上,Ets-1的表达都是下降的。THP-1细胞Ets-1的表达基本不变。ChIP检测发现:各个β3GnT的基因DNA检出谱基本上和第一部分用RT-PCR法检出的β3GnT mRNA的表达谱一致,结合EMSA证实有活化的Ets-1结合至β3GnT-2或/和β3GnT-8基因DNA片段,但未能检测到Ets-1对β3GnT-4的表达调控。
     结论:Ets-1很可能参与HL60和SHI-1细胞株中β3GnT-2和β3GnT-8在ATRA和TPA诱导分化时的表达调控,至少也是调控因素之一。但NB4细胞中的β3GnT不受Ets-1的调节。
A lot of literatures have been reported that the structures of sugar chains (glycans) in cell glycoconjugates were altered during cell malignant transformation or differentiation, and these alterations were caused by the changed expressions of some glycosyltransferases responsible for the synthesis of cell glycans.β1, 3 -acetyl-glucosaminyltransferase (β3GnT) is a family of glycosyltransferase which participates in the synthesis of aβ1, 3-GlcNAc linkage in its products. Among them,β3GnT-2, -4, -8 subtypes are known to syntheis the poly-N-acetyllactosamine structure in the N- or O-linked glycans of glycoproteins. The aim of this study is to investigate the relationship between the expressions of these 3 enzymes and the differentiation of 4 leukemic cell lines. In addition, the regulation ofβ3GnT-2, -4, -8 by transcription factor Ets-1 was also studied.
     This thesis was divided into three parts.
     1. The relation betweenβ3GnT-2, -4, -8 and the differentiation of human acute promelocytic leukemic cells
     Purpose: To study the relation between the expression of glycosyltransferaseβ3GnT-2, -4, -8 and the differentiation of human acute promelocytic leukemic cell lines HL60 and NB4.
     Methods: RT-PCR was used to determine the expressions ofβ3GnT-2, -4, -8 in six different leukemic cell lines. By using ATRA to induce the differentiateion of HL60 and NB4 cell lines toward myelocytes or TPA to induce the differentiateion of these two cell lines toward monocytes, the expression changes ofβ3GnT-2, -4, -8 mRNAs before and after the induced differentiation were measured with Real-time PCR, and accompanied with morphological observation to check the differentiation.
     Results:β3GnT-2 was expressed in leukemic cell lines, SHI-1, THP-1, K562, HL60, U937 and NB4 with different magnitudes.β3GnT-4 was only expressed in NB4 cells. Conversely,β3GnT-8 was not expressed in NB4 only, but expressed on other five cell lines with various degrees. After treated with 10-7mol/L ATRA or 10ng/mlTPA for 2h or 3 days, all of the expressions ofβ3GnT-2, -4, -8 mRNAs were up-regulated with various degrees as compared with the control samples without the addition of inducing agents, especiallyβGnT-4 which was highly increased and show a time-dependent alteration. The elevations ofβ3GnT-8 andβ3GnT-2 were similar. When HL60 and NB4 were differentiated by ATRA toward myelocytes, the up-regulation ofβ3GnTs was more obvious than that using TPA to differentiate two cell lines toward monocytes. In addition, HL60 cells were more sensitive than NB4 cells in the up-regulation ofβ3GnTs by these two differentiation inducers.
     Conclusion: The expressions ofβ3GnT-2, -4, -8 were increased with various degrees in promelocytic leukemic cell lines during diffrentiation toward myelocytes or monocyte with ATRA or TPA. The effect of ATRA was greater than that of TPA; and HL60 cells were more sensitive to the differentiation agents than NB4 cells.
     2. The relation betweenβ3GnT-2, -4, -8 and the differentiation of human monocytic leukemic cells.
     Purpose: To study the relation between the expression ofβ3GnT-2, -4, -8 and the differentiation of human monocytic leukemic cell lines SHI-1 and THP-1.
     Methods: Based on the results of Part-1, two human monocytic leukemia cell lines, SHI-1 and THP-1, were selected. The mRNA expressions ofβ3GnT-2, -4, -8 were further studied in these two cell lines by real-time PCR before and after the treatment of ATRA and TPA, and accompanied with morphological observation.
     Results:β3GnT-2 mRNA was promptly down-regulated after SHI-1 cells were treated with 10-7mol/L ATRA for 2h, but returned to pre-treated level after 3 days. β3GnT-2 mRNA was also elevated after 10ng/ml TPA treatment for 2h and 3 days, especially after 3 days.β3GnT-4 was up regulated at the similar degree ofβ3GnT-2 only on 3 day after TPA treatment; andβ3GnT-8 was slightly increased after ATRA or TPA treatment for 3 days. On the contrast, THP-1 cells were not sensitive to the concentration of both ATRA and TPA that we used, as indicated by the un-changed expressions ofβ3GnT-2, -4, -8 mRNAs. This is in coincidence with the un-alteration in morphological observation.
     Conclusion: Human monocytic leukemic cell lines are less sensitive to ATRA or TPA than human pre-myelocytic cell lines, the changes of the expression ofβ3GnT-2, -4, -8 mRNAs were not apparent as in human pre-myelocytic cells. Between two cell lines, THP-1 cells showed no response to the concentration of both ATRA and TPA that we used,and this results is in accordance with the morphological observation.
     3. Study on the regulation of the expressions ofβ3GnT-2, -4, -8 by transcription factor Ets-1.
     Purpose: To investigate the expression of transcription factor Ets-1 during the induced differentiation of leukemic cells and the role of Ets-1 on the regulation of the transcription ofβ3GnT-2, -4, -8.
     Methods: The expression changes of Ets-1 mRNA were estimated using Real-time PCR after the treatment of ATRA or TPA on four leukemic cell lines, HL60, NB4, SHI-1 and THP-1. The binding of Ets-1 to the gene DNA ofβ3GnTs and the regulation ofβ3GnTs by Ets-1 in HL60, NB4 and SHI-1 cells was further determined by chromatin immuno-precipitation ( ChIP ) method combined with PCR amplification of the sequences of target gene and electrophoresis mobility shift assay (EMSA).
     Results: After the induced differentiation by ATRA or TPA, the expression of Ets-1 mRNA in HL60 cells was up-regulated with different degrees, ATRA was more effective than TPA. Oppositely, Est-1 expression was down-regulated in NB4 and SHI-1 cells after the treatment of ATRA or TPA in general. THP-1 cell line was resistant to both inducer, so its Ets-1 expression was unchanged after the treatment of these inducers. It was found that the detected pattern of the gene DNA ofβ3GnT subtypes using ChIP method combined with PCR amplification and EMSA was consistent to the expressive pattern ofβ3GnT mRNA detected with RT-PCR, and the binding of Ets-1 to the gene fragments ofβ3GnT-2 or/andβ3GnT-8 was certified.
     Conclusion: Ets-1 is probably participate in the up-regulation,at least is one of the regulatory factors ofβ3GnT-2 andβ3GnT-8, during the induced differentiation of HL60 and SHI-1 cells with ATRA or TPA. However, in NB4 cells, the expression changes ofβ3GnTs were not in accordance with the expression change of Ets-1.
引文
1. Chen HL, Guo P, Wang QY. Modification of cell growth, signaling and apoptosis by N-acetylglucosaminyltransferase-V andα1,3fucosyltransferase-VII. Current Drug Target. 2009, in press.
    2. Brockhausen I, Schachter H. Glycosyltransferases involved in N and O-glycan biosynthesis. In: Gabius H J, Gabius S (eds). Glycosciences: Status and perspectives. London, New York, Tokyo: Melbourne Madras: Chapman & Hall, 1997, pp79-112.
    3. Ohtsubo K, Marth JD. Glycosylation in Cellular Mechanisms of Health andDisease. Cell 2006, 126:855-867.
    4. Liu F, Qi Hl, Chen Hl. Regulation of differentiation- and proliferation-inducers on Lewis antigens,α-fucosyltransferase and metastatic potential in hepatocacinoma cells. Brit J Cancer. 2001, 84:1556-1563.
    5. Li Z, Liu AH, Liu F, Chen HL. Modification of pentasaccharide core of surface N-glycans during differentiation of HL-60 cells. Leukemia Res. 1998, 22:727-734.
    6. Liu AH, Liu F, Li Z, Gu JX, Chen HL. Alterations in glycosyltransferases during myeloid and monocytoid differentiation of HL-60 cells. Cell Biology International. 1998, 718:545-550.
    7. Guo P, Chen HJ, Wang QY, Chen HL. Down regulation of N-acetyl- glucosaminyltransferase V facilitates all-trans retinoic acid to induce apoptosis of human hepatocarcinoma cells. Mol Cell Biochem. 2005, 284: 103-110.
    8. Wang QY, Guo P, Duan LL, Shen ZH, Chen HL.α-1,3-Fucosyltransferase-VII stimulates the growth of hepatocarcinoma cells via cyclin dependent kinase inhibitor p27Kip1. Cell Mol Life Sci. 2005, 62: 171-178.
    9. Wang H, Wang QY, Zhang Y, Shen ZH, Chen HL.α1,3 Fucosyltransferase-VII modifies the susceptibility of apoptosis induced by ultraviolet and retinoic acid in human hepatocarcinoma cells. Glycoconj J. 2007, 24: 207-220.
    10. Norihiko Shiraishi, Ayumi Natsume, Akira Togayachi, Tetsuo Endo, Tomohiro Akashima. Identification and Characterization of Three Novelβ1,3-N-Acetylglucosaminyltransferases Structurally Related to theβ1,3-Galactosyltransferase family. J. Biol. Chem,2001, 276(5): 3498-3507.
    11. Dapeng Zhou, Andre Dinter, Ricardo Gutierrez Gallego, Johannis P.Kamerling. Aβ-1,3-N-acetylglucosaminyltransferase with poly-Nacetyllactosaminesynthase activity is structurally related toβ-1,3-galactosyltransferases. Proc. Natl. Acad. Sci. USA, 1999, 96: 406-411.
    12. Akira Togayachi, Tomohiro Akashima, Reiko Ookubo, Takashi Kudo, Shoko Nishihara, et al. Molecular Cloning and Characterization of UDP - GlcNAc: Lactosylceramideβ1,3-N-Acetylglucosaminyltransferase (β3Gn-T5), an Essential Enzyme for the Expression of HNK-1 and Lewis X Epitopes on Glycolipids. J. Biol. Chem., 2001,276: 22032-22040.
    13. Narimatsu H. ( 2006 ) Human glycogene cloning: focus onβ3 - glycosyltransferase andβ4-glycosyltransferase families. Current Opin Struct Biol. 16: 567-575.
    14. Chaochun Huang, Jialiang Zhou, Cloning and tissue distributrion of a the humanβ3GnT8(GalT7) gene, a member of theβ1,3-Glycosyltransferase family. Glyconj. J, 2004, 21: 265-271.
    15. Hiroyasu Ishida, Akira Togayachi, Tokiko Sakai et al A novel beta1,3-N-acetylglucosaminyltransferase ( beta3Gn-T8 ) ,which synthesizes poly-N-acetyllactosamine, is dramatically upregulated in colon cancer. FEBS Lett, 2005, 579(1): 71-78.
    16. Seko A, Yamashita K. Characterization of a novel galactose:β–1 ,
    3-Nacetylglucosaminyltransferase(β3Gn-T8): the complex formation ofβ3Gn-T2 andβ3Gn-T8 enhances enzymatic activity. Glycobiology, 2005, 15: 943-951.
    17. Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood, 2008; 111: 2505-2515.
    18. Hu J, Liu YF, Wu CF, Xu F, Shi ZX, Zhu YM, Li JM, Tang W, Zhao WL, Wu W, Sun HP, Chen QS, Chen B, Zhou GB, Zelent A, Waxman S, Wang ZY, Chen SJ, Chen Z. Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide based therapy in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci USA 2009 [Epub ahead of print]
    19.袁晓莉,林全德,魏旭东.佛波酯对白血病细胞诱导分化的研究进展.白血病.淋巴瘤, 2008 17(2)
    20. Guo HB, Zhang QS, Chen HL. Effects of H-ras and v-sis over-expression on N-acetylglucosa-minyltransferase V and metastasis-related phenotypes in human hepatocarcinoma cells. J Cancer Res Clin Oncol, 2000,126: 263-270.
    21. Guo HB , Liu F, Zhao JH, Chen HL. Down-regulation of N-acetylglucosaminyltransferase V tumorigenesis-or metastasis-suppressor genes and its relation to metastatic phenotypes. J Cell Biochem, 2000,79: 370-385.
    22. Liu Fei, Qi Hui-ling, Zhang Ying, Zhang Xia-ying, Chen Hui-li. Transfection of c- erbB2/neu gene up-regulates the expression of sialyl Lewis X,α1,3 fucosyltransferase VII and metastatic potential in human hepatocarcinoma cell line. Eur J Biochem. 2001, 268: 3501-3512.
    23. Liu Fei, Zhang Ying, Zhang Xia-ying, Chen Hui-li. Transfection of nm23-H1 gene into human hepatocarcinoma cell line inhibits the expression of sialyl Lewis X,α1,3 fucosyl transferase VII and metastatic potential. J Cancer Res Clin Oncol, 2002, 128: 189-196.
    24. Wang, QY, Guo, P, Duan, LL, Shen, ZH, Chen, HL.α-1,3-Fucosyltransferase-VII stimulates the growth of hepatocarcinoma cells via cyclin dependent kinase inhibitor p27Kip1. Cell Mol Life Sci. 2005, 62: 171-178.
    25. Kang R, Saito H, Ihara Y, Miyoshi E, Koyama N, Sheng Y, Taniguchi N. Transcriptional regulation of the N-acetylglucosaminyltransferase V gene in human bile duct carcinoma cells (HuCC-T1) is mediated by Ets-1. J Biol Chem, 1996, 271(43): 26706-26712.
    26. Ko JH, Miyoshi E, Noda K. Regulation of the GnT-V promotor by transcription factor ets-1 in various cancer cell lines. J Biol Chem, 1999, 274(33):22941-22948.
    27. P Guo, Y Zhang, JH Zhao,HB Guo, XY Zhang, and HL Chen. Regulation on the expression and N-glycosylation of integrins by N-acetylglucosaminyltransferase V. Biochem Biophys Res Commun, 2003; 310(2): 619-626.
    28. Tamara Handerson and John M. Pawelek.β1,6-branched Oligosaccharides and Coarse Vesicles: A Common, Pervasive Phenotype in Melanoma and Other Human Cancers. Cancer Res., 2003; 63(17): 5363-5369.
    29. Arun Seth, Dennis K Watson. ETS transcription factorsand their emerging roles in human cancer. European Journal of Cancer, 2005,41: 2462-2478.
    30. Rudd P M, Dwek R A. Glycosylation: Heterogeneity and 3D structure of proteins. In: Farman G D, edi. Critical review in biochemistry and molecular biology. Bo Co Roton, Florida: CRC press, 1997(1): 1-100.
    1.董硕,陈竺,王振义。急性早幼粒细胞白血病的分子生物学研究进展。国外医学.输血及血液学分册,1992, 3:147-149.
    2.秘营昌,王建祥。我国急性白血病的诊断治疗现状。国际输血及血液学杂志。2006, 4:290-291.
    3.陈惠黎。肝细胞诱导分化的研究进展。肿瘤学新理论与新技术。上海科技教育出版社。1997年第1版。308-329.
    4.沈岳奋,柴希运,陈惠黎。佛波酯对人肝癌细胞株酪氨酸蛋白激酶的影响。生物化学与生物物理学报,1993, 25:537-541.
    5.柴希运,沈岳奋,陈惠黎。佛波酯对人肝癌细胞株蛋白激酶C和酪氨酸蛋白激酶的影响。中华肿瘤杂志,1993, 15:182-184.
    6.柴希运,陈惠黎,顾健人。维甲酸和佛波酯对人肿瘤细胞c-myc和IGF-Ⅱ基因表达的相反作用。中国癌症杂志,1994, 4:229-231.
    7.刘爱华,李溪冰,顾建新,陈惠黎。全反式视黄酸对HL-60细胞中N-乙酰氨基葡萄糖转移酶III,IV活力的影响。生物化学与生物物理学报,1997,2:116-121.
    8. Li Z, Liu AH, Liu F, Chen HL. Modification of pentasaccharide core of surface N-glycans during differentiation of HL-60 cells. Leukemia Res, 1998, 22:727-734.
    9. Seko A, Yamashita K. Activation of beta1,3-N-acetylglucosaminyltransferase-2 (beta3Gn-T2) by beta3Gn-T8. Possible involvement of beta3Gn-T8 in increasing poly-N-acetyllactosamine chains in differentiated HL-60 cells. J Biol Chem, 2008, 283(48):33094-33100.
    10.李忠,陈惠黎。蛋白激酶C亚型在HL-60细胞诱导分化中的变化。实验生物学报,1997,30:201-206.
    11.刘飞,刘爱华,陈惠黎。α-1,6-岩藻糖转移酶活力在7721人肝癌细胞及HL-60白血病细胞诱导分化中的变化。上海医科大学学报,1999,2:122-124.
    12. Hagan FK. Ten Hagen KG, Tabak LA. PolypeptideN-Acetylgalactosaminyltransferases. In Taniguchi N, Honde K, Fukuda M. (eds) Handbook of glycosyltransferase and related genes.Tokyo, Springer Chapter 22, pp167-17314.
    13. Ten Hagen KG, Fritz TA, Tabak LA. All in the family: the UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferases. Glycobiology. 2003, 13(1):1R~16R.
    14. Cheng L, Tachibana K, Iwasaki H, Kameyama A, Zhang Y, Kubota T, Hiruma T, Tachibana K, Kudo T, Guo JM, Narimatsu H. Characterization of a novel human UDP-GalNAc transferase, pp-GalNAc-T15. FEBS Lett. 2004, 566(1-3):17-24.
    15. Wandalls HH, Hassan H, Mirgorodskaya E, Kristensen AK, Roepstorff P, Bennett EP, Nielsen PA, Hollingsworth MA, Burchell J, Taylor-Papadimitriou J, Clausen H. Substrate Specificities of three menbers of the human UDP-N-acetyl-D-galactosamine: polypeptide N-acetyl-galactosaminyltransferase family, GalNAc-T1,-T2, and -T3. J Biol Chem 1997, 272: 2350-23514.
    16. Lozzio BB, Lozzio CB. Properties of the K562 cell line derived from a patient with chronic myeloid leukemia. Intern J Cancer 1977, 19: 136-143.
    1. Chen S, Xue Y, Zhang X, Wu Y, Pan J, Wang Y, Ceng J. A new human acute monocytic leukemia cell line SHI-1 with t(6;11)(q27;q23) gene alteration and high tumorigenicity in nude mice. Hematologia 2005, 90:766-775.
    2.陈苏宁,薛永权,吴亚芳,潘金兰,岑建农。人单核细胞白血病细胞系SHI-1的诱导分化和凋亡。白血病.淋巴瘤,2006, 15(6):408-411.
    3. Tsuchiya S, Yamabe M, Yamaguchi Y, Kobayashi Y, Konno T, Tada K. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer. 1980, 26(2):171-176.
    4. Tsuchiya S, Kobayashi Y, Goto Y, Okumura H, Nakae S, Konno T, Tada K.Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res. 1982, 42(4):1530-1536.
    5. Li Z, Liu AH, Liu F, Chen HL. Modification of pentasaccharide core of surface N-glycans during differentiation of HL-60 cells. Leukemia Res, 1998, 22:727-734.
    1. Ioanna G Maroulakou, Damon B Bowe. Expression and function of Ets transcription factors in mammalian development: a regulatory network. Oncogene, 2000, 19:6432-6442.
    2. Arun Seth, Dennis K Watson. ETS transcription factorsand their emerging roles in human cancer. European Journal of Cancer, 2005,41:2462-2478.
    3. Ito Y, Miyoshi E, Takeda T. Expression and possible role of ets-1 in hepatocellular carcinoma. Am J Clin Pathol, 2000, 114(5):719-725.
    4. Kang R, Saito H, Ihara Y, Miyoshi E, Koyama N, Sheng Y, Taniguchi N. Transcriptional regulation of the N-acetylglucosaminyltransferase V gene in human bile duct carcinoma cells (HuCC-T1) is mediated by Ets-1. J Biol Chem, 1996, 271(43):26706-26712.
    5. Ko JH, Miyoshi E, Noda K. Regulation of the GnT-V promotor by transcription factor ets-1 in various cancer cell lines. J Biol Chem, 1999, 274(33):22941-22948.
    6. Sato T, Furukawa K. Sequential action of Ets-1 and Sp1 in the activation of the human beta-1, 4-galactosyltransferase V gene involved in abnormal glycosylation characteristic of cancer cells. J Biol Chem. 2007, 21; 282(38):27702-27712.
    7. Sato T, Furukawa K. Transcriptional regulation of the humanβ-1,4-galactosyltranferase V gene in cancer cells, Essential role of transcription factor Sp1. J Biol Chem. 2004, 279(38): 39574-39853.
    8. Igarashi T, Abe M, Oikawa M, Nukiwa T, Sato Y. Retinoic acids repress the expression of Ets-1 in endothelial cells. Tohoku J.Exp.Med., 2001,194:35-43.
    9. Li R, Pei H, Dennis KW. Regulation of Ets function by protein–protein interactions. Oncogene, 2000, 19:6514-6523.
    [1] Maroulakou IG,Papas TS,Green JE.Differential expression of Ets-1 and Ets-2 proto-oncogenes during murine embryogenesis.Oncogene,1994,9(6):1551.
    [2] Ito Y,Miyoshi E,Takeda T,et a1.Expression and possible role of ets-1 in hepatoeellular carcinoma[J].Am J Clin Pathol,2000,114(5):719-725.
    [3] Yordy JS,MuiseHelmericksRC.Signaltransduction and the Ets family of transcription factors,oncogene,2000,19:6503-6513.
    [4] COwley DO,Graves BJ Phosphorylation represses Ets-1 DNA binding by Reinforcing autoinhibiton.Genes Dev,2000,14:366-376.
    [5] Tian J,Karin M.Stimu1ation of E1kI transcriptional activity by Mitogen- activated protein kinases is negaitvely regulated by protein Phosphatase 2B(calcineuirin).J Biol Chem,1999,274:15173-15180.
    [6] Chang J,Lee C,Hahm KB,Yi Y,Choi SG,Kim SJ.Overexpression of ERTI (ESX/ESE-1/ELF3),an ets-related transcription factor,induces Endogenous TGF-beta typeII receptor expression and restores the TGF-beta signaling pathwayin Hs578t human breast cancer cells.Oncogene,2000,19:151- 154 .
    [7] RameilP,LecineP,GhysdaelJ,GouilleuxF,Kahn-PerlesB,ImbertJ.IL-2 and 1ong-term T cell acitvaiton induce physical and functional interaction between STAT5 and ETS transcription factors in human T cells.Oncogene,2000,19:2086- 2097.
    [8] NgUyen VT,Benveniste EN.Involvement of STAT-l and ets family members ininterferon-gamma induction of CD40 transcirptionin microglia/macrophages J Biol Chem,2000;275:23674-23684.
    [9] Uehwalter G,Gross C,Wasylyk B.Ets ternary complex transcription factors. [J].Gene,2004,324(1):1-14.
    [10] Mattot V,VercamerC Soncin F Calmels T Huguet C FafeurV,Vandenbunder B. Constitutive expression of the DN A-binding domain of Etsl increases endothelialcell adhesion and stimulates their organization into capillary-like structures .Oncogene 2000,19:762-772.
    [11] Lelievre E,Lionneton F,Soncin F,Vandenbunder B.The Ets family contains tran- scriptional activators and repressors involved in angiogenesis.Int,Biochem CPII Biol 2001,33:391-407.
    [12] Kawachi K,Masuyama N,Nishida E.Essential role of the transcription factor Ets-2 in Xenopus early development.Biol Chem 2003,278:5473-5477.
    [13] Vlaeminck-Guillem V,Carrere S,Dewitte F,Stehelin D,Desl X, Duter- queCoquillaud M.The Ets family m ember Erg gene isexpressed in mesodermal tissues and neural crests at fundamental steps during mouse embryogenesis.Mech Dev 2000,91:331-335.
    [14] Spyropoulos DD Pharr PN Lavenburg KR Jackers P Papas Ogawa M,Watson DK.Hemorrhage impaired hematopoiesis and lethality in mouse embryos carrying a targeted disruption of the Flil transcription factor.Mol Cell Biol 2000;20:5643-5652.
    [15] Truong AH,Ben-D avid Y.The role of Fli-1 in norm al cell function and malignant transformation.Oncogene 2000,19:6482-6489.
    [16] Brown LA,Rodaway AR,Schilling IF,Jowett T,Ingham PW,Patient RK,Sharocks AD.Insights into early vasculogenesis revealed by expression of the ETs-domain transcription factor Fli-1 in wild-type and mutant zebrafish embryos.Mech Dev 2000,90:237-252.
    [17] Potter MD, Buijs A,Kreider B,van Rompaey L,Grosveld GC.Identificationan and characterization of a new human ETS- family transcription factor,TEL2,that is expressed in hematopoietic tissues and can associate with TEL1/ETV6.Blood 2000,95:3341-3348.
    [18] Maroulakou IG,Papas TS,Green JE.. Differential expression of Ets-1 andEts-2 proto-oncogenes during murine embryogenesis.Oncogene,1994,9(6):1551.
    [19] Ito Y,Miyoshi E,Takeda T,et al.Ets-1 expression in extrahepatic bileduct carcinoma and cholangiocellular carcinoma.Oncology,2000,58(3):248-252.
    [20] Naito S,Shimizu K,Nakashima M,et al.Overexpression of Ets-1 transcription factor in angiosarcoma of the skin.Pathol Kes PRACT,2000,196(2):103-109.
    [21] Cuili Zhang,Mary M,Angela Lai,et al.Ets-1 protects vascular smoothmusle cells from undergoing apoptosis by activating p21WAF1/ Cip1 transcription via distinct CIS2acting elements in the p21WAF1/ Cip1 promoter.J Bio Chem,2003,10:1074.
    [22] Brass AL,Zhu AQ,Singh H.Assembly requirements of PU.1-Pip(IRF-4)activator complexes:inhibiting function in vivo using fused dimmers.EM BO,1999,18:977—991
    [23] Crowe DL,Shuler CF.Regulation of tumor cell invasion by extrace1lular matrix[J].Histol HiostPathol,1999,14(2):665-671.
    [24] Trojanowska M.Ets factors and regulation of the extracellular matrix.Oncogene,2000,19(55):6464-6471.
    [25] KitangeG , Kishikawa M,Nakayama T,ExPression of the Ets-1 Proto-Oncogene correlates with malignant potential in human astrocytic tumors.ModPathol,1999,12(6):618-626.
    [26] Takai N,Miyazaki T,Fujisawa K et al.ExPression of c-Etsl is associated with Malignant potential in endometiral carclnoma.Cancer,2000,89(10):2059-2067.
    [27] Oikawa T.ETS transcription factors:possible targets for cancer therapy[J].Cancer Sci,2004,95(8):626-633.
    [28] Du ZJ,Kamei M,Suzuki M,et al.Coordinated expression of Ets-1, pERK1/2,and VEGF in retina of streptozotocin-induced diabetic rats.[J].Ophthalmic Res,2007,39(4):224-231.
    [29] Gory S,Dalmon I,Prandini MH,et al.Requirement of a GT box (Sp1 site) and two Ets binding sites for vascular endothelial cadherin gene transcription[J].J Biol Chem,1998,273(12):6750-6755.
    [30] Watanabe D,Takagi H,Suzuma K,et al.Transcription factor Ets-1 Mediates ischemia-and vascular endothelial growth factor-dependent retinal neovascularization[J].Am J Pathol,2004,164(5):1827-1835.
    [31] Hewett PW,Daft EL,Laughton CA,et al.Selective inhibition of the humantie-1 promoter with triplex-forming oligonucleotides targeted to Ets binding sites[J].Mol Med,2006,12(123):8-16.
    [32] Li B,Lager J,Wang D,et al.Ets-1 participates in and facilitates developmental expression of hypoxia-induced mitogenic factor in mouse lung[J].Frony Biosci,2007,12:2269-2278.
    [33] Elvert G,Kappel A,Heidenreich R,et al.Cooperative interaction of Hypoxia-inducible factor-2alpha (HIF-2alpha) and Ets-1 in the tran-scriptional activation of vascular endothelial growth factor receptor-2 ( Flk-1 ) [J].J Biol Chem,2003,278(9):7520-7530.

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