Mahlknecht_2013_Proc.Natl.Acad.Sci.U.S.A_110_8170

Reference

Title : Aptamer to ErbB-2\/HER2 enhances degradation of the target and inhibits tumorigenic growth - Mahlknecht_2013_Proc.Natl.Acad.Sci.U.S.A_110_8170
Author(s) : Mahlknecht G , Maron R , Mancini M , Schechter B , Sela M , Yarden Y
Ref : Proc Natl Acad Sci U S A , 110 :8170 , 2013
Abstract :

Aptamers, oligonucleotides able to avidly bind cellular targets, are emerging as promising therapeutic agents, analogous to monoclonal antibodies. We selected from a DNA library an aptamer specifically recognizing human epidermal growth factor receptor 2 (ErbB-2/HER2), a receptor tyrosine kinase, which is overexpressed in a variety of human cancers, including breast and gastric tumors. Treatment of human gastric cancer cells with a trimeric version (42 nucleotides) of the selected aptamer (14 nucleotides) resulted in reduced cell growth in vitro, but a monomeric version was ineffective. Likewise, when treated with the trimeric aptamer, animals bearing tumor xenografts of human gastric origin reflected reduced rates of tumor growth. The antitumor effect of the aptamer was nearly twofold stronger than that of a monoclonal anti-ErbB-2/HER2 antibody. Consistent with aptamer-induced intracellular degradation of ErbB-2/HER2, incubation of gastric cancer cells with the trimeric aptamer promoted translocation of ErbB-2/HER2 from the cell surface to cytoplasmic puncta. This translocation was associated with a lysosomal hydrolase-dependent clearance of the ErbB-2/HER2 protein from cell extracts. We conclude that targeting ErbB-2/HER2 with DNA aptamers might retard the tumorigenic growth of gastric cancer by means of accelerating lysosomal degradation of the oncoprotein. This work exemplifies the potential pharmacological utility of aptamers directed at cell surface proteins, and it highlights an endocytosis-mediated mechanism of tumor inhibition.

PubMedSearch : Mahlknecht_2013_Proc.Natl.Acad.Sci.U.S.A_110_8170
PubMedID: 23630281

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Citations formats

Mahlknecht G, Maron R, Mancini M, Schechter B, Sela M, Yarden Y (2013)
Aptamer to ErbB-2\/HER2 enhances degradation of the target and inhibits tumorigenic growth
Proc Natl Acad Sci U S A 110 :8170

Mahlknecht G, Maron R, Mancini M, Schechter B, Sela M, Yarden Y (2013)
Proc Natl Acad Sci U S A 110 :8170