Identification of differentially expressed genes involved in the formation of multicellular tumor spheroids by HT-29 colon carcinoma cells

Kleomenis Dardousis, Christian Robert Voolstra, Monic Roengvoraphoj, Asieb Sekandarzad, Senait Mesghenna, Johannes Winkler, Yon Ko, Jürgen Hescheler, Agapios Sachinidis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

The multicellular tumor spheroid (MCTS) model represents a suitable in vitro model recreating in vivo tumor formation. The aim of this study was to identify differentially expressed genes that could potentially serve as predictive gene markers for MCTS and be involved in the formation of MCTS. Using the suppression subtractive hybridization (SSH) method, we identified ERBB2/HER2-interacting protein (Erbin), Tumor rejection gp96 (Tr-gp96), 12S ribosomal RNA (12S rRNA), ATP synthase, Kruppel-like transcription factor 5 (KLF5), transcription factor-like 5 (TCFL5), and the dual-specificity phosphatase 11 (DUSP11) to be overexpressed in 3-day-old HT-29 colon carcinoma MCTSs compared to HT-29 colon carcinoma cells grown in monolayer. We could also confirm overexpression of these genes in HT-29 MCTSs and in MCTSs formed by the human glioblastoma tumor cell lines U343 MG, U373 MG, and DBTRG 05 MG. Knockdown of KLF5, Erbin, DUSP11, and TCFL5 was effectively achieved after transfection of HT-29 cells with the appropriate short-interfering RNAs (siRNAs), and correlated with a significant inhibition of MCTS formation in the case of KLF5, Erbin, and TCFL5 siRNAs. We suggest that KLF5, Erbin, and TCFL5 are essential for MCTS formation and play a key role in the development of tumor diseases.

Original languageEnglish (US)
Pages (from-to)94-102
Number of pages9
JournalMolecular Therapy
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2007

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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