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- W2794407789 abstract "Rapamycin analogs (rapalogs) inhibit mammalian target of rapamycin (mTOR) and are known to cause induction of autophagy and G1 cell cycle arrest. However, it remains unknown whether rapalog-induced autophagy plays a critical role in its regulation of cell cycle. We, for the first time, found that rapalog everolimus could stimulate autophagy-mediated Cyclin D1 degradation in breast cancer cells. Inhibiting mTOR with everolimus rapidly increased the degradation of Cyclin D1 in MCF-10DCIS.COM and MCF-7 cells. 3-Methyladenine (3-MA), a classic autophagy inhibitor, could attenuate everolimus-induced Cyclin D1 degradation. Furthermore, knockdown of autophagy related gene 7 (Atg-7) could also repress everolimus-triggered degradation of Cyclin D1 in MCF-10DCIS.COM. Moreover, everolimus-induced autophagy occurred earlier than its induction of G1 arrest and cell death. Blockade of autophagy attenuated everolimus-induced G1 cell cycle arrest. These preliminary data support the conclusion that the autophagy induced by rapalogs in breast cancer cells appears to cause Cyclin D1 protein degradation resulting in G1 cell cycle arrest. Our findings contribute to our knowledge of the interplay between autophagy and cell cycle regulation mediated by mTOR signaling and Cyclin D1 regulation. Citation Format: Chen G, Ding X-F, Bouamar H, Pressley K, Yang J, Sun L-Z. Rapalog everolimus induces G1 cell cycle arrest through autophagy-mediated protein degradation of cyclin D1 in breast cancer cells [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-04-01." @default.
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- W2794407789 date "2018-02-14" @default.
- W2794407789 modified "2023-09-27" @default.
- W2794407789 title "Abstract P6-04-01: Rapalog everolimus induces G1 cell cycle arrest through autophagy-mediated protein degradation of cyclin D1 in breast cancer cells" @default.
- W2794407789 doi "https://doi.org/10.1158/1538-7445.sabcs17-p6-04-01" @default.
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