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

Takayuki Murata; Seiko Iwata; Mohammed Nure Alam Siddiquey; Tetsuhiro Kanazawa; Fumi Goshima; Daisuke Kawashima; Hiroshi Kimura; Tatsuya Tsurumi

doi:10.1371/journal.pone.0063566

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

Takayuki Murata, Seiko Iwata, Mohammed Nure Alam Siddiquey, Tetsuhiro Kanazawa, Fumi Goshima, Daisuke Kawashima, Hiroshi Kimura, Tatsuya Tsurumi

Research output: Contribution to journal › Article › peer-review

30 Citations (Scopus)

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.

Original language	English
Article number	e63566
Journal	PloS one
Volume	8
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0063566
Publication status	Published - 03-05-2013
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General

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

author = "Takayuki Murata and Seiko Iwata and Siddiquey, {Mohammed Nure Alam} and Tetsuhiro Kanazawa and Fumi Goshima and Daisuke Kawashima and Hiroshi Kimura and Tatsuya Tsurumi",

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Heat Shock Protein 90 Inhibitors Repress Latent Membrane Protein 1 (LMP1) Expression and Proliferation of Epstein-Barr Virus-Positive Natural Killer Cell Lymphoma. / Murata, Takayuki; Iwata, Seiko; Siddiquey, Mohammed Nure Alam; Kanazawa, Tetsuhiro; Goshima, Fumi; Kawashima, Daisuke; Kimura, Hiroshi; Tsurumi, Tatsuya.

In: PloS one, Vol. 8, No. 5, e63566, 03.05.2013.

Research output: Contribution to journal › Article › peer-review

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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

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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.

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

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