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 journalArticle

28 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-2Rγnull (NOG) mice was also retarded. These results suggest that HSP90 inhibitors can be alternative treatments for patients with EBV-positive malignancies.

Original languageEnglish
Article numbere63566
JournalPloS one
Volume8
Issue number5
DOIs
Publication statusPublished - 03-05-2013

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HSP90 Heat-Shock Proteins
Human herpesvirus 4
natural killer cells
tanespimycin
lymphoma
Human Herpesvirus 4
Viruses
membrane proteins
Natural Killer Cells
Lymphoma
Membrane Proteins
T-cells
Oncogene Proteins
Cell proliferation
Tumors
Neoplasms
B-Lymphocytes
Cell Proliferation
T-Lymphocytes
Molecules

All Science Journal Classification (ASJC) codes

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

Cite this

Murata, Takayuki ; Iwata, Seiko ; Siddiquey, Mohammed Nure Alam ; Kanazawa, Tetsuhiro ; Goshima, Fumi ; Kawashima, Daisuke ; Kimura, Hiroshi ; Tsurumi, Tatsuya. / Heat Shock Protein 90 Inhibitors Repress Latent Membrane Protein 1 (LMP1) Expression and Proliferation of Epstein-Barr Virus-Positive Natural Killer Cell Lymphoma. In: PloS one. 2013 ; Vol. 8, No. 5.
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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 journalArticle

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AU - Siddiquey, Mohammed Nure Alam

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