{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:05:21Z","timestamp":1761717921561},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2004,3,19]],"date-time":"2004-03-19T00:00:00Z","timestamp":1079654400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2004,3,19]],"date-time":"2004-03-19T00:00:00Z","timestamp":1079654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Gene Ther"],"published-print":{"date-parts":[[2004,5,1]]},"DOI":"10.1038\/sj.cgt.7700706","type":"journal-article","created":{"date-parts":[[2004,3,19]],"date-time":"2004-03-19T10:45:55Z","timestamp":1079693155000},"page":"309-316","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":141,"title":["Specific downregulation of bcl-2 and xIAP by RNAi enhances the effects of chemotherapeutic agents in MCF-7 human breast cancer cells"],"prefix":"10.1038","volume":"11","author":[{"given":"Raquel T","family":"Lima","sequence":"first","affiliation":[]},{"given":"Lu\u00eds M","family":"Martins","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 E","family":"Guimar\u00e3es","sequence":"additional","affiliation":[]},{"given":"Clara","family":"Sambade","sequence":"additional","affiliation":[]},{"given":"M Helena","family":"Vasconcelos","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2004,3,19]]},"reference":[{"key":"BF7700706_CR1","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/nrc776","volume":"2","author":"FH Igney","year":"2002","unstructured":"Igney FH, Krammer PH . Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer. 2002;2:277\u2013288.","journal-title":"Nat Rev Cancer"},{"key":"BF7700706_CR2","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/nrc883","volume":"2","author":"S Cory","year":"2002","unstructured":"Cory S, Adams JM . The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2:647\u2013656.","journal-title":"Nat Rev Cancer"},{"key":"BF7700706_CR3","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1126\/science.281.5381.1322","volume":"281","author":"JM Adams","year":"1998","unstructured":"Adams JM, Cory S . The Bcl-2 protein family: arbiters of cell survival. Science. 1998;281:1322\u20131326.","journal-title":"Science"},{"key":"BF7700706_CR4","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/nrm830","volume":"3","author":"GS Salvesen","year":"2002","unstructured":"Salvesen GS, Duckett CS . IAP proteins: blocking the road to death's door. Nat Rev Mol Cell Biol. 2002;3:401\u2013410.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BF7700706_CR5","doi-asserted-by":"publisher","first-page":"6627","DOI":"10.1038\/sj.onc.1204087","volume":"19","author":"Z Huang","year":"2000","unstructured":"Huang Z . Bcl-2 family proteins as targets for anticancer drug design. Oncogene. 2000;19:6627\u20136631.","journal-title":"Oncogene"},{"key":"BF7700706_CR6","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1038\/35080103","volume":"2","author":"M Holcik","year":"2001","unstructured":"Holcik M, Korneluk RG . XIAP, the guardian angel. Nat Rev Mol Cell Biol. 2001;2:550\u2013556.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BF7700706_CR7","doi-asserted-by":"publisher","first-page":"3009.1","DOI":"10.1186\/gb-2001-2-7-reviews3009","volume":"2","author":"AM Verhagen","year":"2001","unstructured":"Verhagen AM, Coulson EJ, Vaux DL . Inhibitor of apoptosis proteins and their relatives: IAPs and other BIRPs. Genome Biol. 2001;2:3009.1\u20133009.10.","journal-title":"Genome Biol"},{"key":"BF7700706_CR8","doi-asserted-by":"publisher","first-page":"3247","DOI":"10.1038\/sj.onc.1202569","volume":"17","author":"EC LaCasse","year":"1998","unstructured":"LaCasse EC, Baird S, Korneluk RG, et al. The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene. 1998;17:3247\u20133259.","journal-title":"Oncogene"},{"key":"BF7700706_CR9","doi-asserted-by":"publisher","first-page":"7124","DOI":"10.1073\/pnas.97.13.7124","volume":"97","author":"J-L Wang","year":"2000","unstructured":"Wang J-L, Liu D, Zhang Z-J, et al. Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc Natl Acad Sci USA. 2000;97:7124\u20137129.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BF7700706_CR10","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1038\/sj.leu.2403029","volume":"17","author":"S Shangary","year":"2003","unstructured":"Shangary S, Johnson DE . Recent advances in the development of anticancer agents targeting cell death inhibitors in the Bcl-2 protein family. Leukemia. 2003;17:1470\u20131481.","journal-title":"Leukemia"},{"key":"BF7700706_CR11","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1038\/sj.leu.2403109","volume":"17","author":"XY Pei","year":"2003","unstructured":"Pei XY, Dai Y, Grant S . The proteasome inhibitor bortezomib promotes mitochondrial injury and apoptosis induced by the small molecule Bcl-2 inhibitor HA14-1 in multiple myeloma cells. Leukemia. 2003;17:2036\u20132045.","journal-title":"Leukemia"},{"key":"BF7700706_CR12","doi-asserted-by":"publisher","first-page":"44236","DOI":"10.1074\/jbc.M207578200","volume":"277","author":"CR Arnt","year":"2002","unstructured":"Arnt CR, Chiorean MV, Heldebrant MP, et al. Synthetic Smac\/DIABLO peptides enhance the effects of chemotherapeutic agents by binding XIAP and cIAP1 in situ. J Biol Chem. 2002;277:44236\u201344243.","journal-title":"J Biol Chem"},{"key":"BF7700706_CR13","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/35081168","volume":"411","author":"PM Waterhouse","year":"2001","unstructured":"Waterhouse PM, Wang MB, Lough T . Gene silencing as an adaptative defence against viruses. Nature. 2001;411:834\u2013842.","journal-title":"Nature"},{"key":"BF7700706_CR14","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1101\/gad.880001","volume":"15","author":"PA Sharp","year":"2001","unstructured":"Sharp PA . RNA interference-2001. Genes Dev. 2001;15:485\u2013490.","journal-title":"Genes Dev"},{"key":"BF7700706_CR15","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1002\/1439-7633(20010401)2:4<239::AID-CBIC239>3.0.CO;2-R","volume":"2","author":"T Tuschl","year":"2001","unstructured":"Tuschl T . RNA interference and small interfering RNAs. Chembiochemistry. 2001;2:239\u2013245.","journal-title":"Chembiochemistry"},{"key":"BF7700706_CR16","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/35052556","volume":"2","author":"SM Hammond","year":"2001","unstructured":"Hammond SM, Caudy AA, Hannon GJ . Post-transcriptional gene silencing by double-stranded RNA. Nat Rev Genet. 2001;2:110\u2013119.","journal-title":"Nat Rev Genet"},{"key":"BF7700706_CR17","doi-asserted-by":"publisher","first-page":"E31","DOI":"10.1038\/35000102","volume":"2","author":"JM Bosher","year":"2000","unstructured":"Bosher JM, Labouesse M . RNA interference: genetic wand and genetic watchdog. Nat Cell Biol. 2000;2:E31\u2013E36.","journal-title":"Nat Cell Biol"},{"key":"BF7700706_CR18","first-page":"1509","volume":"7","author":"E Bernstein","year":"2001","unstructured":"Bernstein E, Denli AM, Hannon GJ . The rest is silence. RNA. 2001;7:1509\u20131521.","journal-title":"RNA"},{"key":"BF7700706_CR19","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nrm1129","volume":"4","author":"DM Dykxhoorn","year":"2003","unstructured":"Dykxhoorn DM, Novina CD, Sharp PA . Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol. 2003;4:457\u2013467.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"BF7700706_CR20","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/418252a","volume":"418","author":"BA Sullenger","year":"2002","unstructured":"Sullenger BA, Gilboa E . Emerging clinical applications of RNA. Nature. 2002;418:252\u2013258.","journal-title":"Nature"},{"key":"BF7700706_CR21","doi-asserted-by":"publisher","first-page":"5716","DOI":"10.1038\/sj.onc.1205653","volume":"21","author":"M Wilda","year":"2002","unstructured":"Wilda M, Fuchs U, Wossmann W, et al. Killing of leukemic cells with BCR\/ABL fusion gene by RNA interference (RNAi). Oncogene. 2002;21:5716\u20135724.","journal-title":"Oncogene"},{"key":"BF7700706_CR22","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1182\/blood-2002-06-1685","volume":"101","author":"M Scherr","year":"2003","unstructured":"Scherr M, Battmer K, Winkler T, et al. Specific inhibition of bcr-abl gene expression by small interfering RNA. Blood. 2003;101:1566\u20131569.","journal-title":"Blood"},{"key":"BF7700706_CR23","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/S0014-5793(03)00523-4","volume":"545","author":"C Nieth","year":"2003","unstructured":"Nieth C, Priebsch A, Stege A, et al. Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi). FEBS Lett. 2003;545:144\u2013150.","journal-title":"FEBS Lett"},{"key":"BF7700706_CR24","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/sj.cgt.7700544","volume":"10","author":"DP Cioca","year":"2003","unstructured":"Cioca DP, Aoki Y, Kiyosawa K . RNA interference is a functional pathway with therapeutic potential in human myeloid leukemia cell lines. Cancer Gene Ther. 2003;10:125\u2013133.","journal-title":"Cancer Gene Ther"},{"key":"BF7700706_CR25","doi-asserted-by":"publisher","first-page":"28815","DOI":"10.1074\/jbc.M203828200","volume":"277","author":"M Abdelrahim","year":"2002","unstructured":"Abdelrahim M, Samudio I, Smith III R, et al. Small inhibitory RNA duplexes for Sp1 mRNA block basal and estrogen-induced gene expression and cell cycle progression in MCF-7 breast cancer cells. J Biol Chem. 2002;277:28815\u201328822.","journal-title":"J Biol Chem"},{"key":"BF7700706_CR26","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1124\/mol.63.6.1373","volume":"63","author":"M Abdelrahim","year":"2003","unstructured":"Abdelrahim M, Smith R, Safe S . Aryl hydrocarbon receptor gene silencing with small inhibitory RNA differentially modulates Ah-responsiveness in MCF-7 and HepG2 cancer cells. Mol Pharmacol. 2003;63:1373\u20131381.","journal-title":"Mol Pharmacol"},{"key":"BF7700706_CR27","doi-asserted-by":"publisher","first-page":"31469","DOI":"10.1074\/jbc.C300240200","volume":"278","author":"SM Srinivasula","year":"2003","unstructured":"Srinivasula SM, Gupta S, Datta P, et al. Inhibitor of apoptosis proteins are substrates for the mitochondrial serine protease Omi\/HtrA2. J Biol Chem. 2003;278:31469\u201331472.","journal-title":"J Biol Chem"},{"key":"BF7700706_CR28","doi-asserted-by":"publisher","first-page":"2749","DOI":"10.1038\/sj.onc.1204342","volume":"20","author":"K Friedrich","year":"2001","unstructured":"Friedrich K, Wieder T, Von Haefen C, et al. Overexpression of caspase-3 restores sensitivity for drug-induced apoptosis in breast cancer cell lines with acquired drug resistance. Oncogene. 2001;20:2749\u20132760.","journal-title":"Oncogene"},{"key":"BF7700706_CR29","first-page":"348","volume":"61","author":"X-H Yang","year":"2001","unstructured":"Yang X-H, Sladek TL, Liu X, et al. Reconstitution of caspase 3 sensitizes MCF-7 breast cancer cells to doxorubicin- and etoposide-induced apoptosis. Cancer Res. 2001;61:348\u2013354.","journal-title":"Cancer Res"},{"key":"BF7700706_CR30","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S0304-3835(99)00441-3","volume":"152","author":"MH Vasconcelos","year":"2000","unstructured":"Vasconcelos MH, Beleza SS, Quirk C, et al. Limited synergistic effect of antisense oligonucleotides against bcr-abl and transferrin receptor mRNA in leukemic cells in culture. Cancer Lett. 2000;152:135\u2013143.","journal-title":"Cancer Lett"},{"key":"BF7700706_CR31","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/S0092-8674(01)00274-4","volume":"104","author":"SJ Riedl","year":"2001","unstructured":"Riedl SJ, Renatus M, Schwarzenbacher R, et al. Structural basis for the inhibition of caspase-3 by XIAP. Cell. 2001;104:791\u2013800.","journal-title":"Cell"},{"key":"BF7700706_CR32","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/35065125","volume":"410","author":"SM Srinivasula","year":"2001","unstructured":"Srinivasula SM, Hegde R, Saleh A, et al. A conserved XIAP-interaction motif in caspase-9 and Smac\/DIABLO regulates caspase activity and apoptosis. Nature. 2001;410:112\u2013116.","journal-title":"Nature"},{"key":"BF7700706_CR33","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1002\/ijc.10776","volume":"103","author":"V Bilim","year":"2003","unstructured":"Bilim V, Kasahara T, Hara N, et al. Role of XIAP in the malignant phenotype of transitional cell cancer (TCC) and the therapeutic activity of XIAP antisense oligonucleotides against multidrug-resistant TCC in vitro. Int J Cancer. 2003;103:29\u201337.","journal-title":"Int J Cancer"},{"key":"BF7700706_CR34","first-page":"5659","volume":"60","author":"H Sasaki","year":"2000","unstructured":"Sasaki H, Sheng Y, Kotsuji F, et al. Down-regulation of X-linked inhibitor of apoptosis protein induces apoptosis in chemoresistant human ovarian cancer cells. Cancer Res. 2000;60:5659\u20135666.","journal-title":"Cancer Res"},{"key":"BF7700706_CR35","doi-asserted-by":"publisher","first-page":"3604","DOI":"10.1128\/MCB.21.10.3604-3608.2001","volume":"21","author":"H Harlin","year":"2001","unstructured":"Harlin H, Reffey SB, Duckett CS, et al. Characterization of XIAP-deficient mice. Mol Cell Biol. 2001;21:3604\u20133608.","journal-title":"Mol Cell Biol"},{"key":"BF7700706_CR36","doi-asserted-by":"publisher","first-page":"3700","DOI":"10.1073\/pnas.91.9.3700","volume":"91","author":"K Nakayama","year":"1994","unstructured":"Nakayama K, Nakayama K-I, Negishi I, et al. Targeted disruption of Bcl-2\u03b1\u03b2 in mice: occurrence of gray hair, polycystic kidney disease, and lymphocytopenia. Proc Natl Acad Sci USA. 1994;91:3700\u20133704.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BF7700706_CR37","doi-asserted-by":"publisher","first-page":"12695","DOI":"10.1074\/jbc.271.22.12695","volume":"271","author":"C Borner","year":"1996","unstructured":"Borner C . Diminished cell proliferation associated with the death-protective activity of Bcl-2. J Biol Chem. 1996;271:12695\u201312698.","journal-title":"J Biol Chem"},{"key":"BF7700706_CR38","doi-asserted-by":"crossref","first-page":"3929","DOI":"10.1182\/blood.V95.12.3929","volume":"95","author":"M Konopleva","year":"2000","unstructured":"Konopleva M, Tari AM, Estrov Z, et al. Liposomal Bcl-2 antisense oligonucleotides enhance proliferation, sensitize acute myeloid leukemia to cytosine-arabinoside, and induce apoptosis independent of other antiapoptotic proteins. Blood. 2000;95:3929\u20133938.","journal-title":"Blood"},{"key":"BF7700706_CR39","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1161\/01.RES.88.3.282","volume":"88","author":"B Levkau","year":"2001","unstructured":"Levkau B, Garton KJ, Ferri N, et al. xIAP induces cell-cycle arrest and activates nuclear factor-kB. Circul Res. 2001;88:282\u2013290.","journal-title":"Circul Res"},{"key":"BF7700706_CR40","doi-asserted-by":"publisher","first-page":"7128","DOI":"10.1038\/sj.onc.1204887","volume":"20","author":"CR de Almodovar","year":"2001","unstructured":"de Almodovar CR, Ruiz-Ruiz C, Munoz-Pinedo C, et al. The differential sensitivity of Bcl-2-overexpressing human breast tumor cells to TRAIL or doxorubicin-induced apoptosis is dependent on Bcl-2 protein levels. Oncogene. 2001;20:7128\u20137133.","journal-title":"Oncogene"},{"key":"BF7700706_CR41","first-page":"1161","volume":"9","author":"JM Davis","year":"2003","unstructured":"Davis JM, Navolanic PM, Weinstein-Oppenheimer CR, et al. Raf-1 and bcl-2 induce distinct and common pathways that contribute to breast cancer drug resistance. Clin Cancer Res. 2003;9:1161\u20131170.","journal-title":"Clin Cancer Res"},{"key":"BF7700706_CR42","first-page":"2134","volume":"58","author":"A Pich\u00e9","year":"1998","unstructured":"Pich\u00e9 A, Grim J, Rancourt C, et al. Modulation of Bcl-2 protein levels by an intracellular anti-Bcl-2 single-chain antibody increases drug-induced cytotoxicity in the breast cancer cell line MCF-7. Cancer Res. 1998;58:2134\u20132140.","journal-title":"Cancer Res"},{"key":"BF7700706_CR43","first-page":"3902","volume":"55","author":"C Teixeira","year":"1995","unstructured":"Teixeira C, Reed JC, Pratt MAC . Estrogen promotes chemotherapeutic drug resistance by a mechanism involving Bcl-2 proto-oncogene expression in human breast cancer cells. Cancer Res. 1995;55:3902\u20133907.","journal-title":"Cancer Res"},{"key":"BF7700706_CR44","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1016\/S0959-8049(02)00391-X","volume":"38","author":"D Del Bufalo","year":"2002","unstructured":"Del Bufalo D, Biroccio A, Trisciuoglio D, et al. Bcl-2 has differing effects on the sensitivity of breast cancer cells depending on the antineoplastic drug used. Eur J Cancer. 2002;38:2455\u20132462.","journal-title":"Eur J Cancer"},{"key":"BF7700706_CR45","doi-asserted-by":"publisher","first-page":"4174","DOI":"10.1038\/sj.onc.1203765","volume":"19","author":"M Holcik","year":"2000","unstructured":"Holcik M, Yeh C, Korneluk RG, et al. Translational upregulation of X-linked inhibitor of apoptosis (XIAP) increases resistance to radiation induced cell death. Oncogene. 2000;19:4174\u20134177.","journal-title":"Oncogene"}],"container-title":["Cancer Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/7700706.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/7700706","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/7700706.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T13:12:26Z","timestamp":1647954746000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/7700706"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,3,19]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2004,5,1]]}},"alternative-id":["BF7700706"],"URL":"https:\/\/doi.org\/10.1038\/sj.cgt.7700706","relation":{},"ISSN":["0929-1903","1476-5500"],"issn-type":[{"value":"0929-1903","type":"print"},{"value":"1476-5500","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,3,19]]},"assertion":[{"value":"3 September 2003","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2004","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}