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• W2316672037 abstract "Bmi-1 is a proto-oncogene that has been implicated in the polycomb complex that is required for cell proliferation and the maintenance of stem cells in a variety of tissues and cancers. Bmi-1 expression has been found to be elevated in a variety of tumors and its abundance has been correlated with survival. Previous studies have implicated Bmi-1 as having a role in radioresistance of cancer cells. In the present studies, we have shown that a stably integrated siRNA, which is conditionally regulated by doxycycline, can be used to study the susceptibility of prostate cancer cell line PC3 to radiation injury following a reduction of Bmi-1 expression. Human HEK293 cells were transfected with lentiviral packaging plasmids and the pTRIPZ vector containing an RFP reporter gene upstream of the Bmi-1 siRNA. PC3 cells were stably transduced with the Bmi-1 siRNA via lentivirus and were initially selected for the puromycin resistance. The RFP reporter gene and Bmi-1 siRNA is under control of a tetracycline response element (TRE) and, following the administration of doxycycline, RFP and Bmi-1 siRNA are concomitantly expressed. Studies on the expression of RFP, Bmi-1 RNA expression by RT-PCR and Bmi-1 measurements by western blots confirm the stable conditional expression of Bmi-1 in prostate cancer PC3 cells. The cell cycle analysis, the apoptotic rate and growth rates of the Bmi-1 expressing and non-expressing cell cultures were not significantly different. However, after treatment with 8 Gy x-irradiation, there was a marked increase in cells in the G2/M and in DNA fragmentation in the PC3 cells when Bmi-1 was reduced. There also was a marked decrease in the plating efficacy and in the cloning efficacy in methylcellulose. Perhaps the delineation of the Bmi-1 status of the cells in a biopsy or in the circulating tumor cells of patients with PC can be used to predict the biological behavior and therapeutic response of these cancers. This study was supported by grant DE-FG02–08ER64608 from the DOE. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-368. doi:10.1158/1538-7445.AM2011-LB-368" @default.
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• W2316672037 date "2011-04-15" @default.
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• W2316672037 title "Abstract LB-368: The reduction of Bmi-1 expression increases the sensitivity of prostate cancer the cell line PC3 to X-ray irradiation" @default.
• W2316672037 doi "https://doi.org/10.1158/1538-7445.am2011-lb-368" @default.
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