https://scholars.lib.ntu.edu.tw/handle/123456789/458625
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Chang M.-C. | en_US |
dc.contributor.author | CHI-AN CHEN | en_US |
dc.contributor.author | CHANG-YAO HSIEH | en_US |
dc.contributor.author | CHIEN-NAN LEE | en_US |
dc.contributor.author | Su Y.-N. | en_US |
dc.contributor.author | Hu Y.-H. | en_US |
dc.contributor.author | WEN-FANG CHENG | en_US |
dc.creator | WEN-FANG CHENG;Hu Y.-H.;Su Y.-N.;Lee C.-N.;Hsieh C.-Y.;Chen C.-A.;Chang M.-C. | - |
dc.date.accessioned | 2020-02-14T02:50:01Z | - |
dc.date.available | 2020-02-14T02:50:01Z | - |
dc.date.issued | 2009 | - |
dc.identifier.issn | 0264-6021 | - |
dc.identifier.uri | 2-s2.0-73149108613 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/458625 | - |
dc.description.abstract | Mesothelin, a secreted protein, is overexpressed in some cancers, but its exact function remains unclear. The aim of the present study was to evaluate the possible function of mesothelin. Real-time PCR, RT (reverse transcription)-PCR, cytotoxicity assays, proliferative assays, apoptotic assays by Hoechst staining, detection of active caspases 3 and 7 by flow cytometric analysis, and immunoprecipitation and immunoblotting were performed. Cancer tissues in paclitaxel-resistant ovarian cancer patients expressed higher levels of mesothelin as assessed using real-time PCR than paclitaxel-sensitive ovarian cancer patients (the mean crossing point value change of mesothelin was 26.9±0.4 in the resistant group and 34.3±0.7 for the sensitive group; P<0.001). Mesothelin also protected cells from paclitaxel-induced apoptosis. The protein expression of Bcl-2 family members, such as Bcl-2 and Mcl-1, was significantly increased regardless of whether cells were treated with exogenous mesothelin or were mesothelin-transfectants. Furthermore, mesothelin-treated cells revealed rapid tyrosine phosphorylation of the p85 subunit of PI3K (phosphoinositide 3-kinase) and ERK (extracellular-signal-regulated kinase) 1/2 for enhancing MAPK (mitogen-activated protein kinase) activity. The anti-apoptotic ability was suppressed and the expression of Bcl-2 family in response to mesothelin was altered by inhibiting PI3K activity, but not by inhibiting MAPK activity. Thus mesothelin can inhibit paclitaxel-induced cell death mainly by involving PI3K signalling in the regulation of Bcl-2 family expression. Mesothelin is a potential target in reducing resistance to cytotoxic drugs. ? The Authors Journal compilation ? 2009 Biochemical Society. | - |
dc.relation.ispartof | Biochemical Journal | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | Apoptosis; Apoptotic; Bcl-2 family; Cancer tissues; Caspases; Crossing point; Cytotoxic drugs; Cytotoxicity assays; Extracellular signal-regulated kinase; Flow-cytometric analysis; Hoechst; Immunoblotting; Immunoprecipitations; Induced apoptosis; Mitogen activated protein kinase; Ovarian cancers; Paclitaxel; Phosphoinositide 3-kinase; Protein expressions; Real-time PCR; Reverse transcription; Secreted protein; Transfectants; Tyrosine phosphorylation; Amino acids; Enzyme activity; Phosphatases; Phosphorylation; Proteins; Cell death; caspase 3; caspase 7; mesothelin; mitogen activated protein kinase; paclitaxel; phosphatidylinositol 3 kinase; protein bcl 2; protein mcl 1; animal cell; apoptosis; article; cell proliferation; cell protection; cell survival; clinical article; concentration response; controlled study; cytotoxicity test; drug targeting; enzyme activity; enzyme inhibition; flow cytometry; human; nonhuman; ovary cancer; priority journal; protein expression; protein function; protein phosphorylation; real time polymerase chain reaction; regulatory mechanism; reverse transcription polymerase chain reaction; 1-Phosphatidylinositol 3-Kinase; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Culture Media, Serum-Free; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Humans; Immunoblotting; Membrane Glycoproteins; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Ovarian Neoplasms; Paclitaxel; Proto-Oncogene Proteins c-bcl-2; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Transfection | - |
dc.title | Mesothelin inhibits paclitaxel-induced apoptosis through the PI3K pathway | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1042/BJ20082196 | - |
dc.identifier.scopus | 56601533000 | - |
dc.relation.pages | 449-458 | - |
dc.relation.journalvolume | 424 | - |
dc.relation.journalissue | 3 | - |
item.openairetype | journal article | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
crisitem.author.dept | Obstetrics & Gynecology-NTUH | - |
crisitem.author.dept | Obstetrics & Gynecology | - |
crisitem.author.dept | Obstetrics & Gynecology-NTUH | - |
crisitem.author.dept | Oncology-NTUH | - |
crisitem.author.dept | Obstetrics & Gynecology | - |
crisitem.author.dept | Obstetrics & Gynecology | - |
crisitem.author.dept | Obstetrics & Gynecology-NTUH | - |
crisitem.author.dept | Obstetrics&Gynecology-NTUHHC | - |
crisitem.author.dept | Obstetrics & Gynecology | - |
crisitem.author.dept | Obstetrics & Gynecology-NTUH | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.dept | Oncology | - |
crisitem.author.dept | Surgery-NTUCC | - |
crisitem.author.orcid | 0000-0001-6670-7939 | - |
crisitem.author.orcid | 0000-0002-1725-0407 | - |
crisitem.author.orcid | 0000-0002-3282-6304 | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | NTU Hsin-Chu Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Cancer Center (NTUCC) | - |
顯示於: | 醫學系 |
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