An apoptosis-related gene network induced by novel compound-cRGD in human breast cancer cells.
Resource
FEBS Letters 581 (18): 3517-3522
Journal
FEBS Letters
Journal Volume
581
Journal Issue
18
Pages
3517-3522
Date Issued
2007-07
Author(s)
Huang, Hsuan-Cheng
Chang, Chih-Chin
Chang, Hsin-Yi
Ou, Chern-Han
Chen, Shui-Tein
Huang, Tsui-Chin
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. ? 2007 Federation of European Biochemical Societies.
Subjects
Apoptosis; Caspase; cRGD; Integrin; MCF-7
SDGs
Other Subjects
caspase 4; caspase 7; caspase 9; peptide; apoptosis; article; bioinformatics; breast cancer; cancer cell culture; cancer therapy; cell line; computer program; enzyme activation; extracellular matrix; gene expression; human; human cell; nucleotide sequence; priority journal; proteomics; reverse transcription polymerase chain reaction; signal transduction; Apoptosis; Breast Neoplasms; Caspases; Cell Line, Tumor; Computer Simulation; Gene Expression Regulation; Gene Regulatory Networks; Humans; Hydrophobicity; Ligands; Models, Molecular; Molecular Structure; Oligonucleotide Array Sequence Analysis; Peptides, Cyclic
Type
journal article
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