An apoptosis-related gene network induced by novel compound-cRGD in human breast cancer cells

Tsui Chin Huang, Hsuan Cheng Huang, Chih Chin Chang, Hsin Yi Chang, Chern Han Ou, Chun Hua Hsu, Shui Tein Chen, Hsueh Fen Juan

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Synthetic peptides with the arginine-glycine-aspartate (RGD) motif have been used widely as inhibitors of integrin-ligand interactions to study cell growth, adhesion, migration and differentiation. We designed cyclic-RGD peptide (Tpa-RGDWPC-, cRGD) which could cause cell death in MCF-7 cell line. In order to understand the mechanism involved in cRGD-induced apoptosis, we used microarray, real-time quantitative PCR (Q-PCR) and bioinformatics to study the effects of cRGD on breast cancer cell line MCF-7. By time-series gene expression measurements and our developed software BSIP and GeneNetwork, we reconstructed an apoptosis-related gene network. In the network, caspase-9, located at the upstream, activates downstream effector caspases such as caspase-7, leading to the induction of caspase-4. Combined our previous proteomics data with newly performed docking simulation, it indicated that the cell death induced by cRGD may be triggered through blocking integrin signaling to the extracellular matrix and activation of caspase pathway. This study provides a molecular explanation of cRGD treatment in breast cancer cells and set forth a constructive far-reaching impact on breast cancer therapy.

Original languageEnglish
Pages (from-to)3517-3522
Number of pages6
JournalFEBS Letters
Volume581
Issue number18
DOIs
Publication statusPublished - Jul 24 2007

Keywords

  • Apoptosis
  • Caspase
  • cRGD
  • Integrin
  • MCF-7

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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