Abstract
The survival rate for women with advanced, metastatic breast cancer has not changed significantly for decades. Regardless of effective therapies, many women still experience recurrences of breast cancer after treatment. Chemotherapy with docetaxel (and other anti-cancer reagents) is widely used for the treatment of breast cancer. Despite an initial response to treatment, the sensitivity to anti-cancer reagents decreased. This leads to progressive disease, normally with fatal consequences. We previously demonstrated that ribophorin II (RPN2), which is part of an N-oligosaccharyl transferase complex, regulates the drug resistance in breast cancer cells and silencing of RPN2 by RNAi-based oligonucleotides is a promising approach to overcome the drug-resistant tumor (Honma K. et al., 2008, Nat Med). In the current study, we examined the role of RPN2 in cancer stem cell (CSC) fraction that is responsible for drugresistance and metastasis. Cell sorting coupled with realtime qPCR analysis showed that RPN2 is highly expressed in CSC fraction. Furthermore, RPN2-knockdown in CSC fraction reduced cancer stem cell frequency, as shown by flow cytometric and in vivo tumorigenicity studies. Thus, these results suggest that RPN2 might be a promising novel target toward the cancer stem cell therapy. L3.2
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