pubmed-article:19638344 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:19638344 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
pubmed-article:19638344 | lifeskim:mentions | umls-concept:C0020792 | lld:lifeskim |
pubmed-article:19638344 | lifeskim:mentions | umls-concept:C0034656 | lld:lifeskim |
pubmed-article:19638344 | lifeskim:mentions | umls-concept:C0024623 | lld:lifeskim |
pubmed-article:19638344 | lifeskim:mentions | umls-concept:C0334227 | lld:lifeskim |
pubmed-article:19638344 | lifeskim:mentions | umls-concept:C0017337 | lld:lifeskim |
pubmed-article:19638344 | lifeskim:mentions | umls-concept:C0014582 | lld:lifeskim |
pubmed-article:19638344 | lifeskim:mentions | umls-concept:C1099354 | lld:lifeskim |
pubmed-article:19638344 | lifeskim:mentions | umls-concept:C0599776 | lld:lifeskim |
pubmed-article:19638344 | lifeskim:mentions | umls-concept:C1414990 | lld:lifeskim |
pubmed-article:19638344 | pubmed:issue | 39 | lld:pubmed |
pubmed-article:19638344 | pubmed:dateCreated | 2009-9-21 | lld:pubmed |
pubmed-article:19638344 | pubmed:abstractText | Epirubicin has been widely used for chemotherapeutic treatment of gastric cancer; however, intrinsic and acquired chemoresistance remains an obstacle to successful management. The mechanisms underlying epirubicin resistance are still not well defined. Here we report the construction and application of a partially randomized retrovirus library of 4 x 10(6) small interfering RNAs to identify novel genes whose suppression confers epirubicin resistance in gastric cancer cells SGC7901. From 12 resistant cell colonies, two small interfering RNAs targeting GAS1 (growth arrest-specific 1) and PTEN (phosphatase and tensin homolog), respectively, were identified and validated. We identified a previously unrecognized chemoresistance role for GAS1. GAS1 suppression resulted in significant epirubicin resistance and cross-resistance to 5-fluorouracil and cisplatin in various gastric cancer cell lines. GAS1 suppression promoted multidrug resistance through apoptosis inhibition, partially by up-regulating the Bcl-2/Bax ratio that was abolished by Bcl-2 inhibition. GAS1 suppression induced chemoresistance partially by increasing drug efflux in an ATP-binding cassette transporter and drug-dependent manner. P-glycoprotein (P-gp) and BCRP (breast cancer resistance protein) but not MRP-1 were up-regulated, and targeted knockdown of P-gp and BCRP could partially reverse GAS1 suppression-induced epirubicin resistance. Verapamil, a P-gp inhibitor, could reverse P-gp substrate (epirubicin) but not non-P-gp substrate (5-fluorouracil and cisplatin) resistance in GAS1-suppressed gastric cancer cells. BCRP down-regulation could partially reverse 5-fluorouracil but not cisplatin resistance induced by GAS1 suppression, suggesting 5-fluorouracil but not cisplatin was a BCRP substrate. These results suggest that GAS1 might be a target to overcome multidrug resistance and provide a novel approach to identifying candidate genes that suppress chemoresistance of gastric cancers. | lld:pubmed |
pubmed-article:19638344 | pubmed:language | eng | lld:pubmed |
pubmed-article:19638344 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:19638344 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:19638344 | pubmed:month | Sep | lld:pubmed |
pubmed-article:19638344 | pubmed:issn | 1083-351X | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:KimW EWE | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:FanDaimingD | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:LinXiaX | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:GangYiY | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:LiuZhiguoZ | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:HonghongWangW | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:YaoLipingL | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:ZhangYongguoY | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:QiaoTaidongT | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:LiTingtingT | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:PanYanglinY | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:JinHaifengH | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:ZhaoLinaL | lld:pubmed |
pubmed-article:19638344 | pubmed:author | pubmed-author:HeLijieL | lld:pubmed |
pubmed-article:19638344 | pubmed:issnType | Electronic | lld:pubmed |
pubmed-article:19638344 | pubmed:day | 25 | lld:pubmed |
pubmed-article:19638344 | pubmed:volume | 284 | lld:pubmed |
pubmed-article:19638344 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:19638344 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:19638344 | pubmed:pagination | 26273-85 | lld:pubmed |
pubmed-article:19638344 | pubmed:dateRevised | 2010-11-18 | lld:pubmed |
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pubmed-article:19638344 | pubmed:year | 2009 | lld:pubmed |
pubmed-article:19638344 | pubmed:articleTitle | Identification of GAS1 as an epirubicin resistance-related gene in human gastric cancer cells with a partially randomized small interfering RNA library. | lld:pubmed |
pubmed-article:19638344 | pubmed:affiliation | State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, China. | lld:pubmed |
pubmed-article:19638344 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:19638344 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
entrez-gene:2619 | entrezgene:pubmed | pubmed-article:19638344 | lld:entrezgene |
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