TY - JOUR
T1 - Heat Shock Protein 90 Inhibitors Repress Latent Membrane Protein 1 (LMP1) Expression and Proliferation of Epstein-Barr Virus-Positive Natural Killer Cell Lymphoma
AU - Murata, Takayuki
AU - Iwata, Seiko
AU - Siddiquey, Mohammed Nure Alam
AU - Kanazawa, Tetsuhiro
AU - Goshima, Fumi
AU - Kawashima, Daisuke
AU - Kimura, Hiroshi
AU - Tsurumi, Tatsuya
N1 - Funding Information:
We thank Dr. N. Shimizu for SNK6 and SNT13 cells. Panels of small molecule inhibitors were kindly provided by the Screening Committee of Anticancer Drugs (SCADS), which is supported by a Grant-in-Aid for Scientific Research on Innovative Areas, Scientific Support Programs for Cancer Research, from the Ministry of Education, Culture, Sports, Science and Technology of Japan. We would further like to express our appreciation to T. Kanda & T. Gamano for technical assistance.
PY - 2013/5/3
Y1 - 2013/5/3
N2 - Epstein-Barr virus (EBV) LMP1 is a major oncoprotein expressed in latent infection. It functions as a TNFR family member and constitutively activates cellular signals, such as NFκB, MAPK, JAK/STAT and AKT. We here screened small molecule inhibitors and isolated HSP90 inhibitors, Radicicol and 17-AAG, as candidates that suppress LMP1 expression and cell proliferation not only in EBV-positive SNK6 Natural Killer (NK) cell lymphoma cells, but also in B and T cells. Tumor formation in immuno-defficient NOD/Shi-scid/IL-2Rγnull (NOG) mice was also retarded. These results suggest that HSP90 inhibitors can be alternative treatments for patients with EBV-positive malignancies.
AB - Epstein-Barr virus (EBV) LMP1 is a major oncoprotein expressed in latent infection. It functions as a TNFR family member and constitutively activates cellular signals, such as NFκB, MAPK, JAK/STAT and AKT. We here screened small molecule inhibitors and isolated HSP90 inhibitors, Radicicol and 17-AAG, as candidates that suppress LMP1 expression and cell proliferation not only in EBV-positive SNK6 Natural Killer (NK) cell lymphoma cells, but also in B and T cells. Tumor formation in immuno-defficient NOD/Shi-scid/IL-2Rγnull (NOG) mice was also retarded. These results suggest that HSP90 inhibitors can be alternative treatments for patients with EBV-positive malignancies.
UR - https://www.scopus.com/pages/publications/84877022289
UR - https://www.scopus.com/pages/publications/84877022289#tab=citedBy
U2 - 10.1371/journal.pone.0063566
DO - 10.1371/journal.pone.0063566
M3 - Article
C2 - 23658841
AN - SCOPUS:84877022289
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 5
M1 - e63566
ER -