TY - JOUR
T1 - Upregulation of LMP1 Expression by Histone Deacetylase Inhibitors in an EBV Carrying NPC Cell Line
AU - Nishikawa, Jun
AU - Kis, Lorand L.
AU - Liu, Anquan
AU - Zhang, Xiangning
AU - Takahara, Miki
AU - Bandobashi, Kentaro
AU - Kiss, Csaba
AU - Nagy, Noemi
AU - Okita, Kiwamu
AU - Klein, George
AU - Klein, Eva
N1 - Funding Information:
This work was supported by The Swedish Cancer Society, Sweden, and the Cancer Research Institute/Concern Foundation.
PY - 2004/1
Y1 - 2004/1
N2 - Objectives: In about 60% of Epstein-Barr virus (EBV) carrying nasopharyngeal carcinomas (NPC) LMP1 expressing cells can be detected. The frequency of LMP1 positive cells and the expression level varies from cell to cell in the different tumors. Cell lines derived from EBV positive NPCs loose the virus during in vitro culture. The in vitro infected NPC cell line TWO3-EBV used in our study carries the neomycin-resistance gene containing EBV and expresses low level of LMP1. With this cell line it was thus possible to study the regulation of LMP1 expression by modification of chromatin acetylation state. Study design: The TWO-EBV cell line was treated with n-butyrate (NB) or trichostatin A (TSA). Results: Shown by immunoblotting, the LMP1 level was elevated in the treated samples. Already 2 h after TSA exposure LMP1 expression was higher and it increased up to 24 h. Immunofluorescence staining showed that nearly all cells were LMP1 positive. Neither EBNA2 nor BZLF1 were induced. Tested first 2 h after the treatment, acetylated histone H3 and H4 were already detectable, and their level increased up to 8 h. Chromatin immunoprecipitation (ChIP) verified that the LMP1-promoter (LMP1p) (ED-L1) was acetylated after TSA treatment. Conclusion: EBV carrying epithelial cells do not express EBNA-2. We showed that LMP1 expression was upregulated by histone deacetylase inhibitors in an in vitro infected, EBV carrier NPC cell line.
AB - Objectives: In about 60% of Epstein-Barr virus (EBV) carrying nasopharyngeal carcinomas (NPC) LMP1 expressing cells can be detected. The frequency of LMP1 positive cells and the expression level varies from cell to cell in the different tumors. Cell lines derived from EBV positive NPCs loose the virus during in vitro culture. The in vitro infected NPC cell line TWO3-EBV used in our study carries the neomycin-resistance gene containing EBV and expresses low level of LMP1. With this cell line it was thus possible to study the regulation of LMP1 expression by modification of chromatin acetylation state. Study design: The TWO-EBV cell line was treated with n-butyrate (NB) or trichostatin A (TSA). Results: Shown by immunoblotting, the LMP1 level was elevated in the treated samples. Already 2 h after TSA exposure LMP1 expression was higher and it increased up to 24 h. Immunofluorescence staining showed that nearly all cells were LMP1 positive. Neither EBNA2 nor BZLF1 were induced. Tested first 2 h after the treatment, acetylated histone H3 and H4 were already detectable, and their level increased up to 8 h. Chromatin immunoprecipitation (ChIP) verified that the LMP1-promoter (LMP1p) (ED-L1) was acetylated after TSA treatment. Conclusion: EBV carrying epithelial cells do not express EBNA-2. We showed that LMP1 expression was upregulated by histone deacetylase inhibitors in an in vitro infected, EBV carrier NPC cell line.
KW - Epstein-Barr virus (EBV)
KW - Histone acetylation
KW - Histone deacetylase inhibitor
KW - Latent membrane protein 1 (LMP1)
KW - Nasopharyngeal carcinoma (NPC)
UR - https://www.scopus.com/pages/publications/10744231742
U2 - 10.1023/B:VIRU.0000012268.35297.ff
DO - 10.1023/B:VIRU.0000012268.35297.ff
M3 - Article
C2 - 14739656
AN - SCOPUS:10744231742
SN - 0920-8569
VL - 28
SP - 121
EP - 128
JO - Virus Genes
JF - Virus Genes
IS - 1
ER -