ADAM23 negatively modulates αvβ3 integrin activation during metastasis

摘要: AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO PARP, a nuclear enzyme that detects and binds to DNA single-strand breaks (SSBs), functions as an important modulator of base excision repair (BER). PARP is also involved in cellular recovery from ionizing radiation (IR)-induced damage by initiating signaling network responsible for the preservation genomic stability. protects SSBs induced deteriorating into more deleterious double-strand (DSB) during replication. As result, inhibitors are being developed cancer therapy due their ability sensitize cells DNA-damaging agents. The purpose this study was determine whether MK-4827, novel PARP-1 PARP-2 inhibitor Merck & Co., Inc., enhances radiosensitivity two NSCLC cell lines, A549 (p53 wild type) H1299 null). We examined effect MK-4827 on clonogenic survival showed 1-hour pretreatment followed 24-hour post-radiation treatment with 1 \#956;M substantially increased (Dose Enhancement Factor (DEF) 1.3) lesser extent (DEF = 1.15). Results analysis DSB demonstrated significantly number radiation-induced DSBs, detected basis \#947;-H2AX foci, at early times after irradiation compared only controls. However, measurement activity, based incorporation biotinylated poly(ADP-ribose) onto histone proteins, dramatically reduced enzymatic activity both lines within hour. Overall, we conclude inhibiting BER pathway compromised, leading conversion detrimental which ultimately results enhanced death. Reasons explain differences response between not understood time but may be difference p53 status or our observation typically have smaller proportion S-phase cells. Citation Information: In: Proc Am Assoc Cancer Res; 2009 18-22; CO. Philadelphia (PA): AACR; 2009. Abstract nr 5546.