BMI1 silencing enhances docetaxel activity and impairs antioxidant response in prostate cancer

• DOI: 10.1002/ijc.25522
• Publication Date: 2010-06-21T17:40:34Z
• Authors: Francesco Crea; Maria A. Duhagon ...; Elaine M. Hurt; Suneetha B. Thomas; Romano Danesi; William L. Farrar
• Keywords: BMI1

The BMI1 oncogene promotes prostate cancer (PC) progression. High B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) expression predicts poor prognosis in PC patients. Recent evidence suggests that may also play a role docetaxel chemoresistance. However, mechanisms and clinical significance of BMI1-related chemoresistance have not been investigated. For this purpose, was silenced 2 cell lines (LNCaP DU 145). Cell proliferation apoptosis after treatment were measured. Guanine oxidation assessed by in-cell western. Global gene analysis performed on cells. Oncomine database used to compare vitro data with samples. silencing had no effect but significantly enhanced docetaxel-induced antitumor activity. Gene demonstrated downregulates set antioxidant genes. Docetaxel increased guanine oxidation, whereas the N-acetyl cysteine rescued death. Examination datasets revealed positive correlation expression. BMI1-controlled genes predictive In conclusion, enhances response, thereby allowing survival docetaxel-based chemotherapy. are overexpressed aggressive should be tested as predictors chemotherapy failure.