0.44060.003 and 0.009, respectively. If the dose is increased The surviving fraction of the differences between the two cell populations ht gr He has become. A total of k nnte Cause inhibition of expression of ATM to an increase Hten radiosensitivity in LMP1 Limonin 1180-71-8 positive cells. NPC is very radiosensitive discussion, therefore, radiotherapy or radiotherapy in combination with chemotherapy are the main treatment strategies. However, the two terms is usually due to complications of acquired resistance to the effects of radiotherapy has emerged as a significant barrier to effective therapy accompanied NPC. It was the inhibition of expression of EBV oncoprotein, including normal LMP1 increased Ht the radiation sensitivity in malignant tumors with EBV in vitro and in vivo association reported.
But how to LMP1 radiosensitivity tr Gt in NPC is not yet clear. It is now well known that the ATM protein is an important regulator of signaling DNA-Sch Is ending. Gueven et al. found that epidermal growth factor lymphoblasto 3-Methyladenine 3-MA aware of ionizing radiation, and this by reducing the scale of the ATM protein was accompanied. Down-regulation of ATM protein also sensitized cancer cells of the prostate, which is induced to an increase in apoptosis by radiation. In this study, we demonstrated that LMP1, which is expressed in more than 75% of the F Ll of NPC, k nnte To regulate ATM expression. Erh Hte level of ATM by LMP1 led to a resistance to radiation and decreased levels of ATM by siRNA leads to radiosensitization. These data suggest that the interaction between play and ATM LMP1 in the NPC is an R Ma Gebliche participation in the radiation resistance.
Cumulative data show that the transcription factor NF-kB plays a role Crucial role in cellular Ren protection against a variety of genotoxic agents confinement Lich IR, and the inhibition of NF-kB leads to radiosensitization in radioresistant cancer cells. Using microarray analysis, Amundson et al. showed that from 1238 human genes, 48 inducible by a single dose of irradiation. Interestingly, the gene expression profiles in human keratinocyte cell line radioresistant HK18-IR a specific set of stress-sensitive genes, including 10 � 5% in the activation of NF-kB fits. Although the exact function of these genes NF-kBassociated are unknown, they are able to influence the fate of cells through the cell cycle regulation and DNA repair-Sch To.
The study of these target genes of NF-kB is responsible for the Aufkl Tion of the radiation induced adaptive resistance important. NF-kB has been found that in cells from patients with AT, which are very sensitive to DNA-Sch Termination by IR and UV light-induced defective. Both lead ATM and NF-kB in an increased gap Hten reqs Susceptibility to fractures of the dsDNA. Therefore, the identification of the molecular link between the ATM kinase and NF-kB in tumor signaling response to therapeutic IR to a better amplifier Ndnis result of cellular Ren response to IR and promising new molecular targets for therapy-associated, the resistance of tumors .
Regarding the link between ATM and LMP1 in NPC, we previously reported that LMP1 k Can different signal transduction pathways, the nuclear factor kappa B Ren to go Activate, causing different downstream pathological Ver Changes in cell proliferation, anti- apoptosis and metastasis. Several studies have demonstrated a correlation of ATM with the NF-kB in the radiosensitivity of cells. In a recently published published shall report a direct interaction between ATM and NF-kB p65 in resting cells and Figure 4 is detected. Reporter assay for the ATM Promotoraktivit t. An illustration of the reporter constructs with either wild type or mutated NF-kB binding sites in the region ATMpromoter. B, the luciferase assay performed in Repoter CNE1 and CNE1-LMP1 cells with plasmids of wild-type or mutant-transfected. The relative luciferase activity of t, the normalized