%0 Journal Article %T Inhibition of KSHV-infected primary effusion lymphomas in NOD/SCID mice by gamma-secretase inhibitor. %+ Key Laboratory of Molecular Virology & Immunology (LMVI) %+ Abramson Cancer Center [philadelphia] %+ University of South China (USC) %+ Hospital of the University of Pennsylvania (HUP) %A Lan, Ke %A Murakami, Masanao %A Bajaj, Bharat %A Kaul, Rajeev %A He, Zhiheng %A Gan, Runliang %A Feldman, Michael %A Robertson, Erle S %Z This work was supported by grants from the Leukemia and Lymphoma Society of America and public health service grants from the NCI CA108461, CA091792, A1067037 from the NIAID and DE017338 from the NIDCR (to ESR) and grants from the 100 Talent Program of the Chinese Academy of Sciences and Natural Science Foundation of China (30770098) to (K.L.). K.L. is a special fellow and E.S.R. is a scholar of the Leukemia and Lymphoma Society of America. %< avec comité de lecture %@ 1538-4047 %J Cancer Biology and Therapy %I Taylor & Francis %V 8 %N 22 %P 2136-2143 %8 2009-11 %D 2009 %R 10.4161/cbt.8.22.9743 %M 19783901 %Z Life Sciences [q-bio]/Microbiology and ParasitologyJournal articles %X Primary effusion lymphoma (PEL) is a common cancer in AIDS patients closely associated with Kaposi's sarcoma-associated herpesvirus (KSHV). Previously, we showed that KSHV latency associated nuclear antigen (LANA) stabilizes intracellular activated Notch1 (ICN) involved in maintenance of the malignant phenotype of KSHV infected PEL cells in vitro. The gamma-secretase inhibitor (GSI) which specifically blocks the production of ICN slows down the proliferation of the KSHV infected PEL cell lines BCBL1, BC3 as well as JSC1 in vitro. In this study, we extended these studies to explore the possibility that manipulation of the Notch signaling by GSI would prevent the growth of the PEL tumors in vivo. We observed that the onset of tumorigenesis of KSHV infected PELs was significantly delayed in GSI treated SCID mice harboring the PEL cell lines. We also found that GSI treatment resulted in necrosis as well as apoptosis in tumors generated by the xenotransplanted KSHV positive PEL cell lines. In contrast, GSI had no effect on mice harboring BJAB cells, a KSHV negative Burkitt's lymphoma cell line where ICN levels were negligible. Our study provides further evidence to suggest that targeted downregulation of abnormal Notch signaling has therapeutic potential for KSHV related primary effusion lymphomas. %G English %2 https://riip.hal.science/pasteur-00625300/document %2 https://riip.hal.science/pasteur-00625300/file/Cancer_Biol_Ther.-2009-Lankepdf.pdf %L pasteur-00625300 %U https://riip.hal.science/pasteur-00625300 %~ RIIP %~ RIIP_SHANGHAI