Open AccessTHIS ARTICLE HAS BEEN RETRACTED Epstein–Barr virus‐encoded latent membrane protein 1 activates β‐catenin signaling in B lymphocytes
Author(s) -
Tomita Mariko,
Dewan Md. Zahidunnabi,
Yamamoto Naoki,
Kikuchi Akira,
Mori Naoki
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01121.x
Subject(s) - biology , epstein–barr virus , protein kinase b , transfection , pi3k/akt/mtor pathway , microbiology and biotechnology , gene knockdown , virus , cell culture , cancer research , signal transduction , virology , genetics
The Epstein–Barr virus‐encoded latent membrane protein 1 is considered the Epstein–Barr virus oncogene based on its importance in Epstein–Barr virus‐induced B‐lymphocyte transformation. β‐Catenin is a potential oncogene, and its accumulation has been implicated in a variety of human cancers. Here, we found that β‐catenin protein was highly expressed in Epstein–Barr virus‐immortalized B‐cell lines compared with peripheral blood mononuclear cells from healthy donors. β‐Catenin expression in Epstein–Barr virus‐immortalized B‐cell line decreased following treatment with LY294002, an inhibitor of phosphatidylinositol 3‐kinase. Treatment with LY294002 or knockdown of β‐catenin by small interfering RNA reduced the growth of Epstein–Barr virus‐immortalized B‐cell line. Transient transfection of latent membrane protein 1 expression plasmid increased β‐catenin protein expression and β‐catenin‐dependent transcription. Latent membrane protein 1 deletions mutants lacking the carboxyl‐terminal activating region 1 domain failed to enhance β‐catenin protein expression and β‐catenin‐dependent transcriptional activity. They also failed to increase phosphorylated AKT expression. Dominant‐negative AKT suppressed latent membrane protein 1‐induced β‐catenin‐dependent transcriptional activity. These results suggest that latent membrane protein 1 activates β‐catenin through the phosphatidylinositol 3‐kinase/AKT signaling pathway. Activation of the β‐catenin pathway by Epstein–Barr virus may contribute to the lymphoproliferation characteristic of Epstein–Barr virus‐infected B‐cells. ( Cancer Sci 2009; 100: 807–812)