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PMID: 23658841 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Heat shock protein 90 inhibitors repress latent membrane protein 1 (LMP1) expression and proliferation of Epstein-Barr virus-positive natural killer cell lymphoma.

PloS one ·Vol. 8 ·No. 5 ·2013-00-00 ·Pages e63566

Murata T, Iwata S, Siddiquey MN, Kanazawa T, Goshima F, Kawashima D, Kimura H, Tsurumi T

Abstract

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-2Rγ(null) (NOG) mice was also retarded. These results suggest that HSP90 inhibitors can be alternative treatments for patients with EBV-positive malignancies.

MeSH Terms
Animals Antineoplastic Agents/chemistry,pharmacology B-Lymphocytes/drug effects,immunology,pathology Benzoquinones/chemistry,pharmacology Cell Proliferation/drug effects Epstein-Barr Virus Infections/drug therapy,genetics,immunology,pathology Gene Expression Regulation HSP90 Heat-Shock Proteins/antagonists & inhibitors,genetics,immunology Herpesvirus 4, Human/drug effects,genetics,immunology Humans Immunocompromised Host Killer Cells, Natural/drug effects,immunology,pathology Lactams, Macrocyclic/chemistry,pharmacology Lymphoma/drug therapy,genetics,immunology,pathology Macrolides/chemistry,pharmacology Mice Mice, Inbred NOD Neoplasms, Experimental Signal Transduction Small Molecule Libraries/chemistry,pharmacology T-Lymphocytes/drug effects,immunology,pathology Tumor Burden/drug effects Viral Matrix Proteins/antagonists & inhibitors,genetics,immunology
Chemicals
Antineoplastic Agents Benzoquinones EBV-associated membrane antigen, Epstein-Barr virus HSP90 Heat-Shock Proteins Lactams, Macrocyclic Macrolides Small Molecule Libraries Viral Matrix Proteins tanespimycin monorden
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Murata Takayuki
Division of Virology, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan.
Iwata Seiko
Siddiquey Mohammed Nure Alam
Kanazawa Tetsuhiro
Goshima Fumi
Kawashima Daisuke
Kimura Hiroshi
Tsurumi Tatsuya
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0063566
Published
2013-00-00
Epub
2013-00-03
Pages
e63566
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3643901
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0063566 PMC Full Text View journal details
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