Heat Shock Protein 90 Inhibitors Repress Latent Membrane Protein 1 (LMP1) Expression and Proliferation of Epstein-Barr Virus-Positive Natural Killer Cell Lymphoma

被引：33

作者：

Murata, Takayuki ^{[1
]}

Iwata, Seiko ^{[2
]}

Siddiquey, Mohammed Nure Alam ^{[2
]}

Kanazawa, Tetsuhiro ^{[2
]}

Goshima, Fumi ^{[2
]}

Kawashima, Daisuke ^{[1
]}

Kimura, Hiroshi ^{[2
]}

Tsurumi, Tatsuya ^{[1
]}

机构：

[1] Aichi Canc Ctr, Res Inst, Div Virol, Nagoya, Aichi 464, Japan

[2] Nagoya Univ, Dept Virol, Grad Sch Med, Nagoya, Aichi 4648601, Japan

来源：

PLOS ONE | 2013年 / 8卷 / 05期

关键词：

SIGNAL BINDING-PROTEIN; J-KAPPA; GENE-EXPRESSION; TRANSCRIPTION FACTORS; HSP90; INHIBITORS; HODGKIN LYMPHOMA; DOWN-REGULATION; NK CELLS; B-CELLS; LINES;

D O I：

10.1371/journal.pone.0063566

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 NFkB, 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 immunodefficient NOD/Shi-scid/IL-2R gamma(null) (NOG) mice was also retarded. These results suggest that HSP90 inhibitors can be alternative treatments for patients with EBV-positive malignancies.

引用

页数：6

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