Massively parallel signature sequencing and bioinformatics analysis identifies up-regulation of TGFBI and SOX4 in human glioblastoma.
Massively parallel signature sequencing and bioinformatics analysis identifies up-regulation of TGFBI and SOX4 in human glioblastoma.
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DOI：
10.1371/journal.pone.0010210
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发表时间：
2010-04-19
期刊：
影响因子：
3.7
通讯作者：
Foltz G
中科院分区：
文献类型：
--
作者：
Lin B;Madan A;Yoon JG;Fang X;Yan X;Kim TK;Hwang D;Hood L;Foltz G
对多形性胶质母细胞瘤（GBM）中异常改变的分子通路的全面的基于网络的理解对于开发这种致命疾病的有效治疗方法至关重要。应用下一代测序技术，大规模并行签名测序（MPSS），我们确定了4535个基因，在正常脑和GBM组织之间的差异表达。通过定量PCR证实了3个上调基因CHI 3L 1、CHI 3L 2和FOXM 1以及2个下调基因neurogranin和L1 CAM的表达变化。通路分析显示，TGF- β通路相关基因在GBM肿瘤标本中表达显著上调。对TGF β信号网络的整合途径分析确定了两种由SOX 4（性别决定区Y-box 4）和TGFBI（转化生长因子β诱导）介导的TGF−β信号途径。定量RT-PCR和免疫组织化学染色显示，SOX 4和TGFBI在GBM组织中的表达在RNA和蛋白水平均高于正常脑组织。体外功能研究证实，TGF- β刺激可增加TGFBI和SOX 4的表达，TGF- β受体1激酶的特异性抑制剂可降低其表达。我们的GBM和正常脑组织的MPSS数据库为科学界提供了有用的资源。GBM中非SMAD介导的TGF−β信号通路通过SOX 4和TGFBI（基因ID：7045）起作用的鉴定表明，在开发针对GBM中TGF−β信号的新治疗策略时，除了经典SMAD介导的通路外，还应考虑这些替代通路。最后，构建一个扩展的TGF- β信号网络，在GBM和正常大脑之间覆盖基因表达变化，扩展了我们对GBM生物学的理解。
A comprehensive network-based understanding of molecular pathways abnormally altered in glioblastoma multiforme (GBM) is essential for developing effective therapeutic approaches for this deadly disease. Applying a next generation sequencing technology, massively parallel signature sequencing (MPSS), we identified a total of 4535 genes that are differentially expressed between normal brain and GBM tissue. The expression changes of three up-regulated genes, CHI3L1, CHI3L2, and FOXM1, and two down-regulated genes, neurogranin and L1CAM, were confirmed by quantitative PCR. Pathway analysis revealed that TGF- β pathway related genes were significantly up-regulated in GBM tumor samples. An integrative pathway analysis of the TGF β signaling network identified two alternative TGF−β signaling pathways mediated by SOX4 (sex determining region Y-box 4) and TGFBI (Transforming growth factor beta induced). Quantitative RT-PCR and immunohistochemistry staining demonstrated that SOX4 and TGFBI expression is elevated in GBM tissues compared with normal brain tissues at both the RNA and protein levels. In vitro functional studies confirmed that TGFBI and SOX4 expression is increased by TGF- β stimulation and decreased by a specific inhibitor of TGF- β receptor 1 kinase. Our MPSS database for GBM and normal brain tissues provides a useful resource for the scientific community. The identification of non-SMAD mediated TGF−β signaling pathways acting through SOX4 and TGFBI (GENE ID:7045) in GBM indicates that these alternative pathways should be considered, in addition to the canonical SMAD mediated pathway, in the development of new therapeutic strategies targeting TGF−β signaling in GBM. Finally, the construction of an extended TGF- β signaling network with overlaid gene expression changes between GBM and normal brain extends our understanding of the biology of GBM.
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密歇根分子相互作用（MIMI）：将拼图拼图放在一起。
影响因子：
14.9
作者：
通讯作者：
--
影响因子：
2.3
作者：
Kawataki, T;Naganuma, H;Nukui, H
通讯作者：
Nukui, H
DOI：
10.1186/bcr1604
发表时间：
2006
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Grigoriadis A;Mackay A;Reis-Filho JS;Steele D;Iseli C;Stevenson BJ;Jongeneel CV;Valgeirsson H;Fenwick K;Iravani M;Leao M;Simpson AJ;Strausberg RL;Jat PS;Ashworth A;Neville AM;O'Hare MJ
通讯作者：
O'Hare MJ
DOI：
10.1016/s0736-5748(99)00009-x
发表时间：
1999-08-01
影响因子：
1.8
作者：
Golembieski, WA;Ge, S;Rempel, SA
通讯作者：
Rempel, SA
影响因子：
64.8
作者：
Chin, L.;Meyerson, M.;Aldape, K.;Bigner, D.;Mikkelsen, T.;VandenBerg, S.;Kahn, A.;Penny, R.;Ferguson, M. L.;Gerhard, D. S.;Getz, G.;Brennan, C.;Taylor, B. S.;Winckler, W.;Park, P.;Ladanyi, M.;Hoadley, K. A.;Verhaak, R. G. W.;Hayes, D. N.;Spellman, Paul T.;Absher, D.;Weir, B. A.;Ding, L.;Wheeler, D.;Lawrence, M. S.;Cibulskis, K.;Mardis, E.;Zhang, Jinghui;Wilson, R. K.;Donehower, L.;Wheeler, D. A.;Purdom, E.;Wallis, J.;Laird, P. W.;Herman, J. G.;Schuebel, K. E.;Weisenberger, D. J.;Baylin, S. B.;Schultz, N.;Yao, Jun;Wiedemeyer, R.;Weinstein, J.;Sander, C.;Gibbs, R. A.;Gray, J.;Kucherlapati, R.;Lander, E. S.;Myers, R. M.;Perou, C. M.;McLendon, Roger;Friedman, Allan;Van Meir, Erwin G;Brat, Daniel J;Mastrogianakis, Gena Marie;Olson, Jeffrey J;Lehman, Norman;Yung, W. K. Alfred;Bogler, Oliver;Berger, Mitchel;Prados, Michael;Muzny, Donna;Morgan, Margaret;Scherer, Steve;Sabo, Aniko;Nazareth, Lynn;Lewis, Lora;Hall, Otis;Zhu, Yiming;Ren, Yanru;Alvi, Omar;Yao, Jiqiang;Hawes, Alicia;Jhangiani, Shalini;Fowler, Gerald;San Lucas, Anthony;Kovar, Christie;Cree, Andrew;Dinh, Huyen;Santibanez, Jireh;Joshi, Vandita;Gonzalez-Garay, Manuel L.;Miller, Christopher A.;Milosavljevic, Aleksandar;Sougnez, Carrie;Fennell, Tim;Mahan, Scott;Wilkinson, Jane;Ziaugra, Liuda;Onofrio, Robert;Bloom, Toby;Nicol, Rob;Ardlie, Kristin;Baldwin, Jennifer;Gabriel, Stacey;Fulton, Robert S.;McLellan, Michael D.;Larson, David E.;Shi, Xiaoqi;Abbott, Rachel;Fulton, Lucinda;Chen, Ken;Koboldt, Daniel C.;Wendl, Michael C.;Meyer, Rick;Tang, Yuzhu;Lin, Ling;Osborne, John R.;Dunford-Shore, Brian H.;Miner, Tracie L.;Delehaunty, Kim;Markovic, Chris;Swift, Gary;Courtney, William;Pohl, Craig;Abbott, Scott;Hawkins, Amy;Leong, Shin;Haipek, Carrie;Schmidt, Heather;Wiechert, Maddy;Vickery, Tammi;Scott, Sacha;Dooling, David J.;Chinwalla, Asif;Weinstock, George M.;O'Kelly, Michael;Robinson, Jim;Alexe, Gabriele;Beroukhim, Rameen;Carter, Scott;Chiang, Derek;Gould, Josh;Gupta, Supriya;Korn, Josh;Mermel, Craig;Mesirov, Jill;Monti, Stefano;Nguyen, Huy;Parkin, Melissa;Reich, Michael;Stransky, Nicolas;Garraway, Levi;Golub, Todd;Protopopov, Alexei;Perna, Ilana;Aronson, Sandy;Sathiamoorthy, Narayan;Ren, Georgia;Kim, Hyunsoo;Kong, Sek Won;Xiao, Yonghong;Kohane, Isaac S.;Seidman, Jon;Cope, Leslie;Pan, Fei;Van Den Berg, David;Van Neste, Leander;Yi, Joo Mi;Li, Jun Z.;Southwick, Audrey;Brady, Shannon;Aggarwal, Amita;Chung, Tisha;Sherlock, Gavin;Brooks, James D.;Jakkula, Lakshmi R.;Lapuk, Anna V.;Marr, Henry;Dorton, Shannon;Choi, Yoon Gi;Han, Ju;Ray, Amrita;Wang, Victoria;Durinck, Steffen;Robinson, Mark;Wang, Nicholas J.;Vranizan, Karen;Peng, Vivian;Van Name, Eric;Fontenay, Gerald V.;Ngai, John;Conboy, John G.;Parvin, Bahram;Feiler, Heidi S.;Speed, Terence P.;Socci, Nicholas D.;Olshen, Adam;Lash, Alex;Reva, Boris;Antipin, Yevgeniy;Stukalov, Alexey;Gross, Benjamin;Cerami, Ethan;Wang, Wei Qing;Qin, Li-Xuan;Seshan, Venkatraman E.;Villafania, Liliana;Cavatore, Magali;Borsu, Laetitia;Viale, Agnes;Gerald, William;Topal, Michael D.;Qi, Yuan;Balu, Sai;Shi, Yan;Wu, George;Bittner, Michael;Shelton, Troy;Lenkiewicz, Elizabeth;Morris, Scott;Beasley, Debbie;Sanders, Sheri;Sfeir, Robert;Chen, Jessica;Nassau, David;Feng, Larry;Hickey, Erin;Schaefer, Carl;Madhavan, Subha;Buetow, Ken;Barker, Anna;Vockley, Joseph;Compton, Carolyn;Vaught, Jim;Fielding, Peter;Collins, Francis;Good, Peter;Guyer, Mark;Ozenberger, Brad;Peterson, Jane;Thomson, Elizabeth
通讯作者：
Thomson, Elizabeth