Inhibition of KSHV-infected primary effusion lymphomas in NOD/SCID mice by gamma-secretase inhibitor
Authors: Ke Lan
Michael Feldman
Zhiheng He
Bharat Bajaj
Runliang Gan
Masanao Murakami
Erle S Robertson
Rajeev Kaul
Journal: Cancer Biology & Therapy (2009)
Discipline: CLINICAL MEDICINE
Keywords: Primary effusion lymphoma; Kaposi's sarcoma-associated herpesvirus; Notch signaling; gamma-secretase inhibitor; tumorigenesis
Affiliations: Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, P.R. China.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Figure 3. * Red boxes: The LANA BJAB GSI panel in Figure 3A appears to show an overlap with the Casp3 JSCI mock panel in Figure 3C. Could the authors please check? The panels represent not only different proteins but also different cell lines. ![file] , 
 Figure 2A, 2B and 2C: the beta-actin immunoblots have unexpected similarity between the four figures. Note the different cells and different experiments. ![image] , 
 Two lanes in Figure 6A look similar to two lanes in Figure 6B. Marked with purpleboxes. ![image] , 
 Correction, May 2021, found here: https: www.tandfonline.com doi full 10.1080 15384047.2021.1926127  In the version of u201cInhibition of KSHV infected primary effusion lymphomas in NOD-SCID mice by u03b3-secretase inhibitoru201d by Ke Lan, Masanao Murakami, Bharat Bajaj, Rajeev Kaul, Zhiheng He, Runliang Gan, Michael Feldman, and Erle S. Robertson, published online November 15th 2009, the authors mistakenly duplicated Figure 3A and Figure 3C due to the similar morphologies of the experiments. The authors wish to replace Figure 3A within the literature so that the correct image is displayed. The authors confirm that these corrections do not alter the conclusions of the article. The article and Figure 3A have been updated accordingly. The authors apologize for any inconvenience caused by this error. ,