Mechanisms of the growth-inhibitory effect of the RNase-EGF fused protein against EGFR-overexpressing cells

Sojun Hoshimoto, Masakazu Ueda, Hiromitsu Jinno, Masaki Kitajima, Junichiro Futami, Masaharu Seno

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: We previously showed the usefulness of a fused protein of human pancreatic ribonuclease1 (hRNase1) with human epidermal growth factor (hEGF) for molecular targeting of EGF receptor (EGFR)-overexpressing cells. In this study, the mechanisms underlying the inhibition of cell growth by RNase-EGF fused proteins was confirmed. Materials and Methods: Des.1-7 hRNase1 was genetically fused to hEGF. The fused proteins were expressed and isolated from Escherichia coli. The internalization of hRNase1-hEGF was confirmed by confocal fluorescence microscopy. The growth-inhibitory effect of the fused proteins was evaluated by MTT assay. Results: FITC-labelled hRNase1-hEGF was internalized into EGFR-overexpressing A431 cells. The internalization was not observed in A431 cells pre-treated with hEGF and EGFR-deficient H69 cells. The growth-inhibitory effect of des.1-7 hRNase1-hEGF against A431 cells was statistically significantly more pronounced than that of hRNase1-hEGF. Conclusion: RNase-EGF fused proteins are internalized through EGFR and inhibit cell growth by exerting their ribonucleolytic activity in the cytosol.

Original languageEnglish
Pages (from-to)857-863
Number of pages7
JournalAnticancer research
Volume26
Issue number2 A
Publication statusPublished - Mar 1 2006

Keywords

  • EGF receptor
  • Internalization
  • Ribonuclease
  • Targeting

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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