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K-Ras-independent effects of the farnesyl transferase inhibitor L-744,832 on cyclin B1/Cdc2 kinase activity, G2/M cell cycle progression and apoptosis in human pancreatic ductal adenocarcinoma cells
DC Field | Value | Language |
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dc.contributor.author | 송시영 | - |
dc.date.accessioned | 2019-11-11T05:21:52Z | - |
dc.date.available | 2019-11-11T05:21:52Z | - |
dc.date.issued | 2000 | - |
dc.identifier.issn | 1522-8002 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/171811 | - |
dc.description.abstract | Pancreatic ductal adenocarcinoma is a highly lethal malignancy that is resistant to traditional cytotoxic therapy. High rates of activating codon 12 K-Ras mutations in this disease have generated considerable interest in the therapeutic application of novel farnesyl transferase inhibitors (FTIs). However, a comprehensive analysis of the effects of FTI treatment on pancreatic cancer cells has not been performed. Treatment of five different human pancreatic cancer cell lines with FTI L-744,832 resulted in inhibition of anchorage-dependent growth, with wide variation in sensitivity among different lines. Effective growth inhibition by L-744,832 correlated with accumulation of cells with a tetraploid (4N) DNA content and high levels of cyclin B1/cdc2 kinase activity, implying cell cycle arrest downstream from the DNA damage-inducible G2/M cell cycle checkpoint. In addition, sensitive cell lines underwent apoptosis as evidenced by changes in nuclear morphology and internucleosomal DNA fragmentation. L-744,832 at a concentration of 1 microM additively enhanced the cytotoxic effect of ionizing radiation, apparently by overriding G2/M checkpoint activation. The effects of FTI treatment on cell growth and cell cycle regulation were associated with changes in posttranslational processing of H-Ras and N-Ras, but not K-Ras. The results confirm the potential therapeutic efficacy of FTI treatment in pancreatic cancer, and suggest that farnesylated proteins other than K-Ras may act as important regulators of G2/M cell cycle kinetics. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Neoplasia Press | - |
dc.relation.isPartOf | Neoplasia | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Antineoplastic Agents/pharmacology* | - |
dc.subject.MESH | Apoptosis/drug effects* | - |
dc.subject.MESH | Carcinoma, Ductal, Breast/pathology* | - |
dc.subject.MESH | Cyclin B/metabolism* | - |
dc.subject.MESH | Cyclin B1 | - |
dc.subject.MESH | Enzyme Inhibitors/pharmacology* | - |
dc.subject.MESH | G2 Phase/drug effects | - |
dc.subject.MESH | Genes, ras/physiology* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Methionine/analogs & derivatives* | - |
dc.subject.MESH | Methionine/pharmacology | - |
dc.subject.MESH | Mitosis/drug effects | - |
dc.subject.MESH | Pancreatic Neoplasms/pathology* | - |
dc.title | K-Ras-independent effects of the farnesyl transferase inhibitor L-744,832 on cyclin B1/Cdc2 kinase activity, G2/M cell cycle progression and apoptosis in human pancreatic ductal adenocarcinoma cells | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Si-Young Song | - |
dc.contributor.googleauthor | Ingrid M. Meszoely | - |
dc.contributor.googleauthor | Robert J. Coffey | - |
dc.contributor.googleauthor | Jennifer A. Pietenpol | - |
dc.contributor.googleauthor | Steven D. Leach | - |
dc.identifier.doi | 10.1038/sj.neo.7900088 | - |
dc.contributor.localId | A02035 | - |
dc.relation.journalcode | J02312 | - |
dc.identifier.eissn | 1476-5586 | - |
dc.identifier.pmid | 10935512 | - |
dc.subject.keyword | farnesylation | - |
dc.subject.keyword | cyclin B/cdc2 | - |
dc.subject.keyword | mitosis | - |
dc.subject.keyword | pancreas | - |
dc.subject.keyword | cancer | - |
dc.contributor.alternativeName | Song, Si Young | - |
dc.contributor.affiliatedAuthor | 송시영 | - |
dc.citation.volume | 2 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 261 | - |
dc.citation.endPage | 272 | - |
dc.identifier.bibliographicCitation | Neoplasia, Vol.2(3) : 261-272, 2000 | - |
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