Tetraspanin Family Member,CD82, Regulates Expression of EZH2 via Inactivation of p38 MAPK Signaling in Leukemia Cells |
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| Authors: | Chie Nishioka Takayuki Ikezoe Jing Yang Akihito Yokoyama |
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| Institution: | 1Department of hematology and Respiratory Medicine immunology, Kochi Medical School, Kochi University, Nankoku, Kochi 783–8505, Japan;2Department of immunology, Kochi Medical School, Kochi University, Nankoku, Kochi 783–8505, Japan;Fujita Health University, School of Medicine., JAPAN |
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| Abstract: | PurposeWe recently found that the tetraspanin family member, CD82, which is aberrantly expressed in chemotherapy-resistant CD34+/CD38− acute myelogenous leukemia (AML) cells, negatively regulates matrix metalloproteinase 9, and plays an important role in enabling CD34+/CD38− AML cells to adhere to the bone marrow microenvironment. This study explored novel functions of CD82 that contribute to AML progression.ResultsMicroarray analysis revealed that levels of EZH2 decreased after shRNA-mediated depletion of CD82 in CD34+/CD38− AML cells. Moreover, the antibody-mediated blockade of CD82 in leukemia cells lowered EZH2 expression via activation of p38 MAPK signaling, decreased the amount of EZH2 bound to the promoter regions of the tumor suppressor genes, and inhibited histone H3 lysine 27 trimethylation in these promoter regions, resulting in upregulation of the tumor suppressors at both the mRNA and protein levels. |
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