||Microarray analysis of human breast cancer cells treated with 111In-trastuzumab modified with nuclear localizing signal peptides
Hasegawa, Sumitaka ,
Li, Huizi ,
Morokoshi, Yukie ,
Furukawa, TakakoSaga, Tsuneo
111In-labeled trastuzumab modified with nuclear localizing signal (NLS) peptides (111In-trastuzumab-NLS) is a promising therapeutic agent for cancer cells overexpressing HER2 because it can efficiently deliver an Auger electron emitter 111In into tumor cell nucleus and 111In is highly toxic when it decays in the nucleus. However, to further improve its therapeutic efficacy, better understanding of cellular responses to 111In-trastuzumab-NLS is required. The aim of this study is to identify gene expression signatures of cells treated with 111In-trastuzumab-NLS using microarray technology.Trastuzumab modified with approximately 10 NLS peptides per antibody was generated. Microarray analyses were performed using RNAs isolated from human breast cancer SKBR3 cells treated for 7 days with the treatments including 231.25 MBq of trastuzumab-NLS. Untreated SKBR3 cells were used as control. The identified genes were imported to the Ingenuity Pathway Analysis (IPA) to characterize gene expression and biofunctional changes induced by 111In-trastuzumab-NLS.Microarray data showed that more than 1,200 probes were up-regulated and down-regulated in treatment of 111In-trastuzumab-NLS in comparison with control and revealed that 338 and 520 probes were specifically up-regulated and down-regulated in treatment of 111In-trastuzumab-NLS, respectively. IPA detected molecular and cellular functions affected by treatment of 111In-trastuzumab-NLS, including cell-to-cell signaling and interaction and cell death/survival.Our microarray study identified gene expression signatures of human breast cancer cells treated with 111In-trastuzumab-NLS. These data may be useful for enhancing therapeutic efficacy of 111In-trastuzumab-NLS.
2015 Society of Nuclear Medicine and Molecular Imaging Annual Meeting