Transcriptomics

Dataset Information

17

Long-term Exposure to Sorafenib of Liver Cancer Cells Induces Resistance with Epithelial-to-Mesenchymal Transition, Increased Invasion and Risk of Rebound Growth


ABSTRACT: Sorafenib leads to a survival benefit in patients with advanced hepatocellular carcinoma but its use is hampered by the occurrence of drug resistance. To investigate the molecular mechanisms involved we developed five resistant human liver cell lines in which we studied morphology, gene expression and invasive potential. The cells changed their appearance, lost E-cadherin and KRT19 and showed high expression of vimentin, indicating epithelial-to-mesenchymal transition. Resistant cells showed reduced adherent growth, became more invasive and lost liver-specific gene expression. Furthermore, following withdrawal of sorafenib, the resistant cells showed rebound growth, a phenomenon also found in patients. This cell model was further used to investigate strategies for restoration of sensitivity to sorafenib. We determined gene expression profiles for 13 samples, grown in 1x106 in 25 cm² tissue flasks. Three flasks contained control samples: HepG2 cells at 20% O2/ 5% CO2/ 75% N2, not exposed to sorafenib. Four flasks contained samples from condition 1: HepG2S1 cells at 20% O2/ 5% CO2/ 75% N2, exposed to sorafenib. Three flasks contained samples from condition 2: HepG2S1 cells at 20% O2/ 5% CO2/ 75% N2, withdrawn from sorafenib. Three flasks contained samples from condition 3: HepG2S1 cells at 2% O2/ 5% CO2/ 93% N2, exposed to sorafenib.

ORGANISM(S): Homo sapiens  

SUBMITTER: Jeroen Dekervel   Petra Windmolders  Eric Van Cutsem  Jos van Pelt  Wouter Van Delm  Hannah van Malenstein  Frederik Nevens  Chris Verslype 

PROVIDER: E-GEOD-62813 | ArrayExpress | 2016-03-14

SECONDARY ACCESSION(S): GSE62813PRJNA265197

REPOSITORIES: GEO, ArrayExpress

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Long-term exposure to sorafenib of liver cancer cells induces resistance with epithelial-to-mesenchymal transition, increased invasion and risk of rebound growth.

van Malenstein Hannah H   Dekervel Jeroen J   Verslype Chris C   Van Cutsem Eric E   Windmolders Petra P   Nevens Frederik F   van Pelt Jos J  

Cancer letters 20121027 1


Sorafenib leads to a survival benefit in patients with advanced hepatocellular carcinoma but its use is hampered by the occurrence of drug resistance. To investigate the molecular mechanisms involved we developed five resistant human liver cell lines in which we studied morphology, gene expression and invasive potential. The cells changed their appearance, lost E-cadherin and KRT19 and showed high expression of vimentin, indicating epithelial-to-mesenchymal transition. Resistant cells showed red  ...[more]

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