Keratin23 (KRT23) knockdown decreases proliferation and affects the DNA damage response of colon cancer cells: KRT23 in human colon cancer

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  • Karin Birkenkamp-Demtröder
  • Stephan Hahn, Molecular GI-Oncology, Center of Clinical Research, Ruhr-University of Bochum, Universitätsstraße 150, D-44480 Bochum, Germany, Germany
  • Francisco Mansilla, Denmark
  • Kasper Thorsen
  • Abdelouahid Maghnouj, Molecular GI-Oncology, Center of Clinical Research, Ruhr-University of Bochum, Universitätsstraße 150, D-44480 Bochum, Germany, Germany
  • Rikke Christensen
  • Bodil Øster, Denmark
  • Torben Falck Ørntoft
Keratin 23 (KRT23) is strongly expressed in colon adenocarcinomas but absent in normal colon mucosa. Array based methylation profiling of 40 colon samples showed that the promoter of KRT23 was methylated in normal colon mucosa, while hypomethylated in most adenocarcinomas. Promoter methylation correlated with absent expression, while increased KRT23 expression in tumor samples correlated with promoter hypomethylation, as confirmed by bisulfite sequencing. Demethylation induced KRT23 expression in vitro. Expression profiling of shRNA mediated stable KRT23 knockdown in colon cancer cell lines showed that KRT23 depletion affected molecules of the cell cycle and DNA replication, recombination and repair. In vitro analyses confirmed that KRT23 depletion significantly decreased the cellular proliferation of SW948 and LS1034 cells and markedly decreased the expression of genes involved in DNA damage response, mainly molecules of the double strand break repair homologous recombination pathway. KRT23 knockdown decreased the transcript and protein expression of key molecules as e.g. MRE11A, E2F1, RAD51 and BRCA1. Knockdown of KRT23 rendered colon cancer cells more sensitive to irradiation and reduced proliferation of the KRT23 depleted cells compared to irradiated control cells.
Original languageEnglish
JournalP L o S One
Volume8
Issue9
ISSN1932-6203
DOIs
Publication statusPublished - 9 Sep 2013

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