DC Field | Value | Language |
---|---|---|
dc.contributor.author | Choi, Junyoung | - |
dc.contributor.author | Yoon, Shinkyo | - |
dc.contributor.author | Kim, Deokhoon | - |
dc.contributor.author | Moon, Yong Wha | - |
dc.contributor.author | Lee, Chang Hoon | - |
dc.contributor.author | Seo, Seyoung | - |
dc.contributor.author | Cheon, Jaekyung | - |
dc.contributor.author | Gho, Yong Song | - |
dc.contributor.author | Kim, Changhoon | - |
dc.contributor.author | Lee, Eung Ryoung | - |
dc.contributor.author | Kim, Soo-Youl | - |
dc.contributor.author | Lee, Kyoungmin | - |
dc.contributor.author | Ha, Joo Young | - |
dc.contributor.author | Park, Sook Ryun | - |
dc.contributor.author | Kim, Sang-We | - |
dc.contributor.author | Park, Kang-Seo | - |
dc.contributor.author | Lee, Dae Ho | - |
dc.date.accessioned | 2019-12-06T07:10:13Z | - |
dc.date.available | 2019-12-06T07:10:13Z | - |
dc.date.created | 2019-09-24 | - |
dc.date.issued | 2019-08 | - |
dc.identifier.issn | 2156-6976 | - |
dc.identifier.uri | https://oasis.postech.ac.kr/handle/2014.oak/100445 | - |
dc.description.abstract | The non-small cell lung cancer (NSCLC) patients with EGFR-sensitive mutations can be therapeutically treated by EGFR-TKI such as erlotinib and gefitinib. However, about 40% of individuals harboring EGFR-TKI sensitive mutations are still resistant to EGFR-TKI. And, it has been reported that both PTEN loss and NF-kappa B activation contribute to intrinsic EGFR-TKI resistance in EGFR-mutant lung cancer. Transglutaminse 2 (TG2) is post-translational modification enzyme and known to induce degradation of tumor suppressors including PTEN and I kappa B alpha with peptide cross-linking activity. Because TG2 was known as a regulator of PTEN and I kappa B alpha (NF-kappa B inhibitor) level in cytosol, we have explored if TG2 can be another key regulator to the intrinsic resistance of EGFR-TKI in the intrinsic EGFR-TKI resistant NSCLC cell. We first found that higher TG2 expression level and lower PTEN and I kappa B alpha expression levels in the intrinsic EGFR-TKI resistant NSCLC compare with EGFR-TKI sensitive NSCLC. TG2 stably expressing EGFR-TKI sensitive NSCLC cells harboring EGFR mutations showed reduction of both PTEN and IkBa and exhibited EGFR-TKI resistance. In reverse, When TG2 is downregulated by TG2 inhibitor in H1650, intrinsic EGFR-TKI resistant NSCLC cell harboring EGFR sensitive mutation, reversed EGFR-TKI resistance via I kappa B alpha restoration. Moreover, combination treatment of TG2 inhibitor and EGFR-TKI decreased the tumor growth in mouse xenograft models of EGFR mutant NSCLCs. Therefore, we have demonstrated that TG2 elicits the intrinsic EGFR-TKI resistance via PTEN loss and activation of NF-kappa B pathway. These results suggest that TG2 may be a useful predictive marker and also be a target for overcoming the resistance. | - |
dc.language | English | - |
dc.publisher | E-CENTURY PUBLISHING CORP | - |
dc.relation.isPartOf | AMERICAN JOURNAL OF CANCER RESEARCH | - |
dc.title | Transglutaminase 2 induces intrinsic EGFR-TKI resistance in NSCLC harboring EGFR sensitive mutations | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.identifier.bibliographicCitation | AMERICAN JOURNAL OF CANCER RESEARCH, v.9, no.8, pp.1708 - 1721 | - |
dc.identifier.wosid | 000483966600014 | - |
dc.citation.endPage | 1721 | - |
dc.citation.number | 8 | - |
dc.citation.startPage | 1708 | - |
dc.citation.title | AMERICAN JOURNAL OF CANCER RESEARCH | - |
dc.citation.volume | 9 | - |
dc.contributor.affiliatedAuthor | Gho, Yong Song | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | CELL LUNG-CANCER | - |
dc.subject.keywordPlus | TYROSINE KINASE INHIBITORS | - |
dc.subject.keywordPlus | TISSUE TRANSGLUTAMINASE | - |
dc.subject.keywordPlus | ERLOTINIB RESISTANCE | - |
dc.subject.keywordPlus | DRUG-RESISTANCE | - |
dc.subject.keywordPlus | RECEPTOR GENE | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | GROWTH | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | SURVIVAL | - |
dc.subject.keywordAuthor | Non-small cell lung cancer | - |
dc.subject.keywordAuthor | transglutaminse 2 | - |
dc.subject.keywordAuthor | epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) | - |
dc.subject.keywordAuthor | combination therapy | - |
dc.subject.keywordAuthor | drug resistance | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.description.journalRegisteredClass | scie | - |
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