Authors: Aeyung Kim DongKi Choi EunSil Sung Jee Sun Yun MyungHee Kwon YongSung Kim
Publish Date: 2012/04/03
Volume: 17, Issue: 2, Pages: 413-419
Abstract
We previously isolated an interfering transbody 4MH2 which penetrated the cytosol of living cells and preferentially hydrolyzed the target Her2 ErbB2 mRNA resulting in Her2 gene silencing followed by apoptotic cell death in Her2overexpressing breast cancer cells Here we report the apoptotic cell death mechanism mediated by 4MH2induced Her2 gene silencing in Her2overexpressing SKBR3 breast cancer cells in comparison with a small interfering RNA siRNA targeting Her2 mRNA Her218siRNA 4MH2 induced G0/G1 cell cycle arrest to cause apoptotic cell death in SKBR3 cells by triggering specific signaling pathways associated with Her2 knockdown including upregulation of G0/G1 cell cycle arrestassociated p21Cip1 and p27Kip1 downregulation of cyclin D1 inhibition of Akt phosphorylation and downregulation of antiapoptotic BclxL which are comparable to those mediated by Her218siRNA Our results suggest that 4MH2mediated Her2 gene silencing can trigger the downstream signaling pathways caused by Her2 downregulation comparable to those mediated by the corresponding siRNA
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