, we have shown that radiation upregulated telomerase activity in Ly-294002-treated glioma cells at the same time as in untreated controls, irrespective of their PTEN status, evidencing a PI3K/AKT independent pathway of telomerase activation. High-grade gliomas are recognized for their inter- and intra-patient heterogeneity. They express diversely telomerase activity and telomerase sub-units, but this expression is strongly correlated to their progression in malignancy plus a poor clinical outcome (38,39,42,69-71). Our study tends to indicate that the method of radiosensitization of high-grade gliomas really should combine distinctive approaches and really should be adapted towards the individual qualities with the tumor in particular with regards to their telomerase status. Several preceding reports have shown that inhibition in the PI3K/AKT pathways radiosensitize gliomas (13,15,32,33), regularly with all the activation of PI3K/AKT conferring radioresistance (7). Ionizing radiation has been shown to raise Akt phosphorylation in many cell lines which includes gliomas (32,72). Having said that, we did not discover any radiationincrease of AKT phosphorylation in our two glioma cells, regularly using the study by Li et al (32) displaying that AKT phosphorylation occurred only in a subset of glioblastoma cells. Ly-294002 induced a G1 arrest in each CB193 and T98G cells in accordance with all the significance in the PI3K/AKT signaling for G1/S transition (73-75). Furthermore, as previously reported in other cell lines (76,77), inhibition from the PI3K/ AKT pathway resulted in an accumulation in G2/M phase, but only after irradiation. Inhibition from the PI3K pathway has been shown to impair DNA repair just after ionizing radiation, suggesting that the blocking in the G2/M transition and subse-MILLET et al: REGULATION OF TELOMERASE ACTIVITY IN IRRADIATED HIGH-GRADE GLIOMASquent cell death could outcome from an inhibition of DSB repair (13,78). Nonetheless, this is not fully sustained by our present study showing that the G2/M arrest was correlated using a delay in DSBs repair only in T98G but not in CB193 cells, following the treatment with Ly-294002. Activation of AKT has been also shown to market G2/M transition via the activation of downstream molecules including cyclin B linked kinase, NF-Y, Chk1 and FOXO3A (79-81).279236-77-0 supplier Our information recommend that beside attainable inhibition of DNA repair depending on the cellular context, Ly-294002 inhibits the signaling pathway expected to pass the G2/M checkpoint independently of DNA repair completion in irradiated cells.2-Bromo-5-(difluoromethyl)pyrazine Data Sheet Irradiation has been shown to upregulate telomerase activity in a variety of cell lines (35,50-53) including a glioblastoma cell line (46).PMID:33554285 AKT is capable to phosphorylate hTERT, the catalytic subunit of telomerase and activate telomerase activity (47). Lately, AKT has been also shown to facilitate nuclear import of hTERT (82). Moreover, ionizing radiation has been reported to upregulate telomerase activity in cancer cell lines by post-translational mechanism by means of the PI3K/AKT pathway (54). Even though Ly-294002 decreased telomerase activity in unirradiated CB193 and T98G cells, concomitantly with AKT dephosphorylation and G1 arrest, we’ve got shown that it did not stop the radiation-induced boost of telomerase activity, which was not correlated with a rise of AKT phosphorylation in these cell lines. These final results rule out a predominant role with the PI3K/AKT pathway inside the radiationinduced upregulation of telomerase activity in our glioma cells lines suggesting that an altern.