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Liver cancer cell lines distinctly mimic the metabolic gene expression pattern of the corresponding human tumours

Nwosu, Z. C.; Battello, N.; Rothley, M. 1; Piorońska, W.; Sitek, B.; Ebert, M. P.; Hofmann, U.; Sleeman, J. 1; Wölfl, S.; Meyer, C.; Megger, D. A. 1; Dooley, S.
1 Karlsruher Institut für Technologie (KIT)


Background: Although metabolism is profoundly altered in human liver cancer, the extent to which experimental models, e.g. cell lines, mimic those alterations is unresolved. Here, we aimed to determine the resemblance of hepatocellular carcinoma (HCC) cell lines to human liver tumours, specifically in the expression of deregulated metabolic targets in clinical tissue samples.
Methods: We compared the overall gene expression profile of poorly-differentiated (HLE, HLF, SNU-449) to well-differentiated (HUH7, HEPG2, HEP3B) HCC cell lines in three publicly available microarray datasets. Three thousand and eighty-five differentially expressed genes in ≥2 datasets (P < 0.05) were used for pathway enrichment and gene ontology (GO) analyses. Further, we compared the topmost gene expression, pathways, and GO from poorly differentiated cell lines to the pattern from four human HCC datasets (623 tumour tissues). In well- versus poorly differentiated cell lines, and in representative models HLE and HUH7 cells, we specifically assessed the expression pattern of 634 consistently deregulated metabolic genes in human HCC. These data were complemented by quantitative PCR, proteomics, metabolomics and assessment of response to thirteen metabolism-targeting compounds in HLE versus HUH7 cells.
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Verlagsausgabe §
DOI: 10.5445/IR/1000085876
Veröffentlicht am 24.09.2018
DOI: 10.1186/s13046-018-0872-6
Zitationen: 89
Web of Science
Zitationen: 85
Zitationen: 98
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2018
Sprache Englisch
Identifikator ISSN: 0392-9078, 1756-9966
KITopen-ID: 1000085876
HGF-Programm 47.01.01 (POF III, LK 01) Biol.Netzwerke u.Synth.Regulat. ITG+ITC
Erschienen in Journal of experimental & clinical cancer research
Verlag Springer Fachmedien Wiesbaden
Band 37
Heft 1
Seiten Art. Nr.: 211
Vorab online veröffentlicht am 03.09.2018
Schlagwörter Omics, Tumour metabolism, Well-differentiated, Poorly differentiated, Metabolic vulnerability, Selective therapy, Biomarkers, MAPK/Ras signaling, Hepatocellular carcinoma
Nachgewiesen in Dimensions
Web of Science
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