Radiation-induced upregulation of telomerase activity escapes PI3-kinase inhibition in two malignant glioma cell lines.

作者: P. MILLET , C. GRANOTIER , O. ETIENNE , F.D. BOUSSIN

DOI: 10.3892/IJO.2013.1970

关键词: TelomerasePI3K/AKT/mTOR pathwayDNA repairCancer researchBiologyTelomerase reverse transcriptaseCell cycleMolecular biologyTelomereGliomaCancer cell

摘要: Tumor relapse after radiotherapy is a great concern in the treatment of high-grade gliomas. Inhibition PI3-kinase/AKT pathway known to radiosensitize cancer cells and delay their DNA repair irradiation. In this study, we show that radiosensitization CB193 T98G, two glioma cell lines, by PI3K inhibitor LY294002, correlates with induction G1 G2/M arrest, but inconsistently linked delayed double-strand break (DSBs) repair. The PI3K/AKT has been shown activate radioprotective factors such as telomerase, whose inhibition may contribute cells. However, radiation upregulates telomerase activity LY-294002-treated well untreated controls, demonstrating PI3K/AKT-independent activation. Our study suggests radiosensitizing strategies based on PI3-kinase gliomas be optimized additional treatments targeting either or telomere maintenance.

参考文章(88)
Fuhui Huang, Hiroshi Kanno, Isao Yamamoto, Yi Lin, Yoshinobu Kubota, Correlation of clinical features and telomerase activity in human gliomas. Journal of Neuro-oncology. ,vol. 43, pp. 137- 142 ,(1999) , 10.1023/A:1006258817785
Liana De Vecchis, Maria Chiara Massara, Mario Turriziani, Enzo Bonmassar, Anna Cardillo, Lucio Tentori, Francesco Torino, Mario Roselli, Paola Nasuti, Anna Maria Di Giacomo, Residual telomerase activity: a marker of cell survival after exposure to gamma radiation in vitro. Anticancer Research. ,vol. 23, pp. 4561- 4569 ,(2003)
C.J. Vlahos, W.F. Matter, K.Y. Hui, R.F. Brown, A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). Journal of Biological Chemistry. ,vol. 269, pp. 5241- 5248 ,(1994) , 10.1016/S0021-9258(17)37680-9
Kwok-Kin Wong, Sandy Chang, Sarah R. Weiler, Shridar Ganesan, Jayanta Chaudhuri, Chengming Zhu, Steven E. Artandi, Karl Lenhard Rudolph, Geoffrey J. Gottlieb, Lynda Chin, Frederick W. Alt, Ronald A. DePinho, Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nature Genetics. ,vol. 26, pp. 85- 88 ,(2000) , 10.1038/79232
Ken D. Aldape, Russell O. Pieper, Tomoko Ozawa, Mitchel S. Berger, Dennis F. Deen, Yukihiko Sonoda, Akt pathway activation converts anaplastic astrocytoma to glioblastoma multiforme in a human astrocyte model of glioma Cancer Research. ,vol. 61, pp. 6674- 6678 ,(2001)
Anne Menet, Cornelia Speth, Clara Larcher, Wolfgang M. Prodinger, Michael G. Schwendinger, Philippe Chan, Michael Jäger, Fritz Schwarzmann, Heidrun Recheis, Marc Fontaine, Manfred P. Dierich, Epstein-Barr Virus Infection of Human Astrocyte Cell Lines Journal of Virology. ,vol. 73, pp. 7722- 7733 ,(1999) , 10.1128/JVI.73.9.7722-7733.1999
Yonehiro Kanemura, Hirotaka Matsumura, Shoju Hiraga, Norio Arita, Takanori Ohnishi, Eiji Miyahara, Shuichi Izumoto, Telomerase Activity and Alterations in Telomere Length in Human Brain Tumors Cancer Research. ,vol. 58, pp. 2117- 2125 ,(1998)
Daniel Basila, Daphne A. Haas-Kogan, David Stokoe, Christian H. Brandts, Alexander R. Gottschalk, Michelle Wong, Nicholas M. Dean, p27Kip1 is required for PTEN-induced G1 growth arrest. Cancer Research. ,vol. 61, pp. 2105- 2111 ,(2001)