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1000 Titel
  • Determining the effects of trastuzumab, cetuximab and afatinib by phosphoprotein, gene expression and phenotypic analysis in gastric cancer cell lines
1000 Autor/in
  1. Ebert, Karolin |
  2. Zwingenberger, Gwen |
  3. Barbaria, Elena |
  4. Keller, Simone |
  5. Heck, Corinna |
  6. Arnold, Rouven |
  7. Hollerieth, Vanessa |
  8. Mattes, Julian |
  9. Geffers, Robert |
  10. Raimúndez, Elba |
  11. Hasenauer, Jan |
  12. Luber, Birgit |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-10-28
1000 Erschienen in
1000 Quellenangabe
  • 20(1):1039
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s12885-020-07540-7 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594334/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Background!#!Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of cancer death worldwide. The molecular mechanisms of action for anti-HER-family drugs in gastric cancer cells are incompletely understood. We compared the molecular effects of trastuzumab and the other HER-family targeting drugs cetuximab and afatinib on phosphoprotein and gene expression level to gain insights into the regulated pathways. Moreover, we intended to identify genes involved in phenotypic effects of anti-HER therapies.!##!Methods!#!A time-resolved analysis of downstream intracellular kinases following EGF, cetuximab, trastuzumab and afatinib treatment was performed by Luminex analysis in the gastric cancer cell lines Hs746T, MKN1, MKN7 and NCI-N87. The changes in gene expression after treatment of the gastric cancer cell lines with EGF, cetuximab, trastuzumab or afatinib for 4 or 24 h were analyzed by RNA sequencing. Significantly enriched pathways and gene ontology terms were identified by functional enrichment analysis. Furthermore, effects of trastuzumab and afatinib on cell motility and apoptosis were analyzed by time-lapse microscopy and western blot for cleaved caspase 3.!##!Results!#!The Luminex analysis of kinase activity revealed no effects of trastuzumab, while alterations of AKT1, MAPK3, MEK1 and p70S6K1 activations were observed under cetuximab and afatinib treatment. On gene expression level, cetuximab mainly affected the signaling pathways, whereas afatinib had an effect on both signaling and cell cycle pathways. In contrast, trastuzumab had little effects on gene expression. Afatinib reduced average speed in MKN1 and MKN7 cells and induced apoptosis in NCI-N87 cells. Following treatment with afatinib, a list of 14 genes that might be involved in the decrease of cell motility and a list of 44 genes that might have a potential role in induction of apoptosis was suggested. The importance of one of these genes (HBEGF) as regulator of motility was confirmed by knockdown experiments.!##!Conclusions!#!Taken together, we described the different molecular effects of trastuzumab, cetuximab and afatinib on kinase activity and gene expression. The phenotypic changes following afatinib treatment were reflected by altered biological functions indicated by overrepresentation of gene ontology terms. The importance of identified genes for cell motility was validated in case of HBEGF.
1000 Sacherschließung
lokal Cetuximab/administration
lokal Phosphoproteins/metabolism [MeSH]
lokal Stomach Neoplasms/pathology [MeSH]
lokal Trastuzumab/administration
lokal Afatinib/administration
lokal Cell Movement [MeSH]
lokal Phosphoproteins/genetics [MeSH]
lokal Apoptosis [MeSH]
lokal Tumor Cells, Cultured [MeSH]
lokal Stomach Neoplasms/drug therapy [MeSH]
lokal Gene expression
lokal Phenotype [MeSH]
lokal Cell and molecular biology
lokal Research Article
lokal Trastuzumab
lokal Gastric cancer
lokal Stomach Neoplasms/genetics [MeSH]
lokal Afatinib
lokal Cell Proliferation [MeSH]
lokal Phosphoprotein
lokal Humans [MeSH]
lokal Stomach Neoplasms/metabolism [MeSH]
lokal Gene Expression Regulation, Neoplastic/drug effects [MeSH]
lokal Antineoplastic Combined Chemotherapy Protocols/pharmacology [MeSH]
lokal Biomarkers, Tumor/metabolism [MeSH]
lokal Biomarkers, Tumor/genetics [MeSH]
lokal Cetuximab
lokal Gene Expression Profiling [MeSH]
lokal Motility
lokal Cell Cycle [MeSH]
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/RWJlcnQsIEthcm9saW4=|https://frl.publisso.de/adhoc/uri/WndpbmdlbmJlcmdlciwgR3dlbg==|https://frl.publisso.de/adhoc/uri/QmFyYmFyaWEsIEVsZW5h|https://frl.publisso.de/adhoc/uri/S2VsbGVyLCBTaW1vbmU=|https://frl.publisso.de/adhoc/uri/SGVjaywgQ29yaW5uYQ==|https://frl.publisso.de/adhoc/uri/QXJub2xkLCBSb3V2ZW4=|https://frl.publisso.de/adhoc/uri/SG9sbGVyaWV0aCwgVmFuZXNzYQ==|https://frl.publisso.de/adhoc/uri/TWF0dGVzLCBKdWxpYW4=|https://frl.publisso.de/adhoc/uri/R2VmZmVycywgUm9iZXJ0|https://frl.publisso.de/adhoc/uri/UmFpbcO6bmRleiwgRWxiYQ==|https://frl.publisso.de/adhoc/uri/SGFzZW5hdWVyLCBKYW4=|https://frl.publisso.de/adhoc/uri/THViZXIsIEJpcmdpdA==
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1000 Erstellt am 2023-11-16T05:35:51.143+0100
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