title: Inhibition of Shc/Grb2 protein-protein interaction suppresses growth of B104-1-1 tumors xenografted in nude mice.
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.
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, 52 Uendong Yusung Taejon, 305-333, Republic of Korea.
authors.forename: Hyae-Kyeong
authors.initials: HK
authors.lastname: Kim
authors.forename: Moon-Jin
authors.initials: MJ
authors.lastname: Jeong
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Kong
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Han
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Son
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Su Hyung
authors.initials: SH
authors.lastname: Hong
authors.forename: Byoung-Mog
authors.initials: BM
authors.lastname: Kwon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology / Q000627:therapeutic use*; D051380:GRB2 Adaptor Protein / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000187:drug effects*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000903:Antibiotics, Antineoplastic; D003609:Dactinomycin; D051380:GRB2 Adaptor Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C495949:Grb2 protein, mouse; C528024:SHC1 protein, human; C528034:Shc1 protein, mouse