title: Heat shock protein 90 inhibitors repress latent membrane protein 1 (LMP1) expression and proliferation of Epstein-Barr virus-positive natural killer cell lymphoma.
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.
authors: Division of Virology, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan.
authors: Takayuki
authors: T
authors: Murata
authors: Seiko
authors: S
authors: Iwata
authors: Mohammed Nure Alam
authors: MN
authors: Siddiquey
authors: Tetsuhiro
authors: T
authors: Kanazawa
authors: Fumi
authors: F
authors: Goshima
authors: Daisuke
authors: D
authors: Kawashima
authors: Hiroshi
authors: H
authors: Kimura
authors: Tatsuya
authors: T
authors: Tsurumi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D047029:Lactams, Macrocyclic / Q000737:chemistry / Q000494:pharmacology*; D008223:Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018942:Macrolides / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D016688:Mice, Inbred NOD; D009374:Neoplasms, Experimental; D015398:Signal Transduction; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018942:Macrolides; D054852:Small Molecule Libraries; D014763:Viral Matrix Proteins; C112765:tanespimycin; C035359:monorden
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