期刊
CANCER SCIENCE
卷 103, 期 4, 页码 821-827出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1349-7006.2012.02221.x
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类别
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
- Ministry of Health, Labour and Welfare of Japan
- MEXT
- Grants-in-Aid for Scientific Research [22590367, 23590417, 23590993, 21592146] Funding Source: KAKEN
Paclitaxel (also known as taxol) is a member of the taxane class of anticancer agents, which has a well-known mechanism that blocks cell mitosis and kills tumor cells, that is often used in clinics to treat cancer. However, some carcinomas such as breast, ovarian and non-small-cell lung cancers are often resistant to paclitaxel treatment. In this study, we used a lentiviral siRNA library against the entire human genomes to identify genes associated with sensitivity to paclitaxel. We isolated two paclitaxel-resistant clones carrying the siRNA specific to septin 10 (SEPT10) and to budding uninhibited by benzimidazoles 3. The relation of budding uninhibited by benzimidazoles 3 to paclitaxel sensitivity has already been established, but that of SEPT10 remains unknown. Interestingly, overexpression of SEPT10 increased cells sensitivity to paclitaxel; we also found that SEPT10 is an important regulator for microtubule stability. Furthermore, we found that paclitaxel-resistant tumors had decreased expression of SEPT10. Thus, SEPT10 may be a novel candidate molecule that acts as a good indicator of paclitaxel-resistant carcinomas (Cancer Sci 2012; 103: 821827)
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