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 language | English |
|---|---|
| Article number | e63566 |
| Journal | PloS one |
| Volume | 8 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 03-05-2013 |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
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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
TY - JOUR
T1 - Heat Shock Protein 90 Inhibitors Repress Latent Membrane Protein 1 (LMP1) Expression and Proliferation of Epstein-Barr Virus-Positive Natural Killer Cell Lymphoma
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
PY - 2013/5/3
Y1 - 2013/5/3
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84877022289&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877022289&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0063566
DO - 10.1371/journal.pone.0063566
M3 - Article
C2 - 23658841
AN - SCOPUS:84877022289
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 5
M1 - e63566
ER -