Degradation of HER2/neu by ANT2 shRNA suppresses migration and invasiveness of breast cancer cells

• Main Authors: Kim Chul-Woo, Jeon Yoon-Kyung, Jang Ji-Young
• Format: Article
• Language: English
• Published: BMC 2010-07-01
• Series: BMC Cancer
• Online Access: http://www.biomedcentral.com/1471-2407/10/391

<p>Abstract</p> <p>Background</p> <p>In breast cancer, the HER2/<it>neu </it>oncoprotein, which belongs to the epidermal growth factor receptor family, may trigger activation of the phosphoinositide-3 kinase (PI3K)/Akt pathway, which controls cell proliferation, survival, migration, and invasion. In this study, we examined the question of whether or not adenine nucleotide translocase 2 (ANT2) short hairpin RNA (shRNA)-mediated down-regulation of HER2<it>/neu </it>and inhibitory effects on the PI3K/Akt signaling pathway suppressed migration and invasiveness of breast cancer cells.</p> <p>Methods</p> <p>We utilized an ANT2 vector-based RNA interference approach to inhibition of ANT2 expression, and the HER2/<it>neu-</it>overexpressing human breast cancer cell line, SK-BR3, was used throughout the study.</p> <p>Results</p> <p>In this study, ANT2 shRNA decreased HER2/<it>neu </it>protein levels by promoting degradation of HER2/<it>neu </it>protein through dissociation from heat shock protein 90 (HSP90). As a result, ANT2 shRNA induced inhibitory effects on the PI3K/Akt signaling pathway. Inhibition of PI3K/Akt signaling by ANT2 shRNA caused down-regulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF) expression, decreased matrix metalloproteinase 2 (MMP2) and MMP9 activity, and suppressed migration and invasion of breast cancer cells.</p> <p>Conclusions</p> <p>These results indicate that knock-down of ANT2 by shRNA down-regulates HER2/<it>neu </it>through suppression of HSP90's function and inhibits the PI3K/Akt signaling pathway, resulting ultimately in suppressed migration and invasion of breast cancer cells.</p>