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| Content Provider | Springer Nature Link |
|---|---|
| Author | Mori, Michihiro Miyamoto, Tomoyuki Yakushiji, Hiromasa Ohno, Setsuyo Miyake, Yasuyuki Sakaguchi, Takuya Hattori, Manabu Hongo, Atsushi Nakaizumi, Akihiko Ueda, Masatsugu Ohno, Eiji |
| Copyright Year | 2011 |
| Abstract | Endometrial cancer is one of the most common gynecological malignancies in Japan, where the disease shows an increasing morbidity. However, surgical therapy remains the treatment of choice for endometrial cancers that tend to be insensitive to radiation therapy and chemotherapy. Therefore, novel therapeutic strategies are required. The Notch signaling pathway regulates embryogenesis and cellular development, but deregulated Notch signaling may contribute to tumorigenesis in several cancers. Moreover, γ-secretase inhibitors have been shown to be potent inhibitors of the Notch signaling pathway; they suppress cellular proliferation and induce apoptosis in several cancer cells. In the present study, we investigated the effect of N-[N-(3, 5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT, γ-secretase inhibitor) on the cell proliferation and apoptosis in Ishikawa endometrial cancer cells. Real-time PCR detected mRNA derived from NOTCH1 and HES1, which are target genes of the Notch signaling pathway, in Ishikawa endometrial cancer cells. After blocking Notch signaling, cellular proliferation decreased, accompanied by increased expression of p21 mRNA and decreased expression of the cyclin A protein. Furthermore, blockade of Notch signaling induced apoptosis. These results suggest that the Notch signaling pathway may be involved in cell proliferation through cell cycle regulation and apoptosis in Ishikawa endometrial cancer cells. Inhibition of the Notch signaling pathway by γ-secretase inhibitors is expected to be a potential target of novel therapeutic strategies for endometrial cancer. |
| Starting Page | 9 |
| Ending Page | 15 |
| Page Count | 7 |
| File Format | |
| ISSN | 09147470 |
| Journal | Human Cell |
| Volume Number | 25 |
| Issue Number | 1 |
| e-ISSN | 17490774 |
| Language | English |
| Publisher | Springer Japan |
| Publisher Date | 2011-12-22 |
| Publisher Place | Japan |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Apoptosis Cell proliferation Endometrial neoplasms N-[N-(3, 5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester Notch1 Embryology Cell Biology Cell Culture Stem Cells Reproductive Medicine Oncology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Cancer Research |
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