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Title 

Inhibition of Shc/Grb2 protein-protein interaction suppresses growth of B104-1-1 tumors xenografted in nude mice

 

Shc/Grb2 상호작용 저해 및 항암효과

Authors 

Hyae Kyeong KimM J JeongMi Young KongM Y HanKwang Hee SonHwan Mook KimS H HongByoung-Mog Kwon

Publisher 

Elsevier

Issue Date 

2005

Citation 

Life Sciences, vol. 78, no. 3, pp. 321-328

Keywords 

actinomycinAnti-tumorErbB-2Grb2Shcgrowth factor receptor bound protein 2mitogen activated protein kinase 1mitogen activated protein kinase 3protein Shccell cycle G1 phase

Abstract 

Actinomycin D was revealed as an inhibitor of Shc/Grb2 interaction in cell lines from our recent study. Shc and Grb2 proteins are important molecules in Ras signaling pathways leading to cellular differentiation and proliferation, which require dramatic morphological changes. It was detected by transmission electron microscopy that actinomycin D induced significant changes in cellular ultrastructures of B104-1-1 cells and confirmed that the changes were due to inhibition of Shc/Grb2 interaction by actinomycin D rather than its inhibitory effect on transcription. Because actinomycin D was dispersed mainly in cytoplasm and Shc peptide (synthetic 13 amino acid tyrosine phosphorylated polypeptide) successfully displaced actinomycin D binding to its cellular targets while the other polypeptide from PDGF receptor could not. We examined the effect of actinomycin D on growth of B104-1-1 tumor xenografted in nude mice. Tumor growth was inhibited in vivo after treatment with this inhibitor. Efficacy was correlated with a reduction in the levels of Shc/Grb2 binding in excised tumors. These results suggest that actinomycin D inhibited Shc/Grb2 interaction in B104-1-1 tumor xenografted in nude mice.

ISSN 

0024-3205

Link 

http://dx.doi.org/10.1016/j.lfs.2005.04.067

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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