Proteomic analysis of a novel compound─cyclic RGD in breast carcinoma cell line MCF-7

• Main Authors: I Hsiu Wang, 王怡琇
• Other Authors: Hsueh-Fen Juan
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/46231910293949373346

碩士 === 國立臺北科技大學 === 化學工程系碩士班 === 92 === Synthetic peptides containing the RGD (Arg-Gly-Asp) motif have been extensively used as inhibitors of integrin-ligand interactions in studies of cell adhesion, migration, growth, differentiation, and apoptosis. The RGD motif is an integrin-recognition motif found in many ligands, so the RGD-containing peptides can be used to probe integrin functions in various biological systems. A linear RGD is tripeptide consists of a flexible structure that makes the motif binding to acceptor with inefficient chelating affinity. Therefore, we designed a cyclic-RGD peptide (Tpa-RGDWPC, cRGD) with rigid skeleton to bind closely to its acceptor. The cRGD was obtained by solid phase peptide synthesis method using Rink amide resin. We showed that the cRGD exerts more potency than that of liner RGD on inhibiting cell growth of MCF-7. This has stimulated us to address the question of how cRGD inhibits cell growth of MCF-7 cells. To uncover what molecular mechanism involved in the RGD motif exert in MCF-7 cells is also of considerable importance. We used proteomics and bioinformatics to survey global changes in proteins after cRGD treatment in MCF-7 cells. The classification of these proteins according to the different biological processes in which they are involved is shown. It is of interest that most of the proteins which appear to be strongly influenced by cRGD treatment are mostly involved in metabolism, cell growth, responsive to external stimulus, cell communication, reproduction and cell death. This is the first report which monitored the protein expression profile of MCF-7 cells in response to treatment with cRGD in a time-course analysis. The clustering data indicated temporal patterns of altered protein expression that can be classified as early, intermediate and late response proteins. These patterns of protein expression may be important for predicting response to cRGD. Taken together, these results demonstrated the molecular explanation for the properties of cRGD in breast cancer cells and provide a valuable in-depth impact in breast cancer therapy.