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dc.contributor.authorXu, W
dc.contributor.authorWang, S
dc.contributor.authorChen, Q
dc.contributor.authorZhang, Y
dc.contributor.authorNi, P
dc.contributor.authorWu, X
dc.contributor.authorZhang, J
dc.contributor.authorQiang, F
dc.contributor.authorLi, A
dc.contributor.authorRøe, Oluf Dimitri
dc.contributor.authorXu, S
dc.contributor.authorWang, M
dc.contributor.authorZhang, R.
dc.contributor.authorZhou, J.
dc.date.accessioned2019-11-07T09:48:51Z
dc.date.available2019-11-07T09:48:51Z
dc.date.created2014-08-29T13:00:38Z
dc.date.issued2014
dc.identifier.issn2041-4889
dc.identifier.urihttp://hdl.handle.net/11250/2627126
dc.description.abstractCisplatin is a cytotoxic platinum compound that triggers DNA crosslinking induced cell death, and is one of the reference drugs used in the treatment of several types of human cancers including gastric cancer. However, intrinsic or acquired drug resistance to cisplatin is very common, and leading to treatment failure. We have recently shown that reduced expression of base excision repair protein XRCC1 (X-ray repair cross complementing group1) in gastric cancerous tissues correlates with a significant survival benefit from adjuvant first-line platinum-based chemotherapy. In this study, we demonstrated the role of XRCC1 in repair of cisplatin-induced DNA lesions and acquired cisplatin resistance in gastric cancer by using cisplatin-sensitive gastric cancer cell lines BGC823 and the cisplatin-resistant gastric cancer cell lines BGC823/cis-diamminedichloridoplatinum(II) (DDP). Our results indicated that the protein expression of XRCC1 was significantly increased in cisplatin-resistant cells and independently contributed to cisplatin resistance. Irinotecan, another chemotherapeutic agent to induce DNA damaging used to treat patients with advanced gastric cancer that progressed on cisplatin, was found to inhibit the expression of XRCC1 effectively, and leading to an increase in the sensitivity of resistant cells to cisplatin. Our proteomic studies further identified a cofactor of 26S proteasome, the thioredoxin-like protein 1 (TXNL1) that downregulated XRCC1 in BGC823/DDP cells via the ubiquitin-proteasome pathway. In conclusion, the TXNL1-XRCC1 is a novel regulatory pathway that has an independent role in cisplatin resistance, indicating a putative drug target for reversing cisplatin resistance in gastric cancer.nb_NO
dc.language.isoengnb_NO
dc.publisherSpringer Naturenb_NO
dc.rightsNavngivelse-Ikkekommersiell-DelPåSammeVilkår 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/deed.no*
dc.titleTXNL1-XRCC1 pathway regulates cisplatin-induced cell death and contributes to resistance in human gastric cancernb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.volume5nb_NO
dc.source.journalCell Death & Diseasenb_NO
dc.source.issue2nb_NO
dc.identifier.doi10.1038/cddis.2014.27
dc.identifier.cristin1150367
dc.description.localcodeThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/nb_NO
cristin.unitcode194,65,15,0
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1


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