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MDM2 regulates a novel form of incomplete neoplastic transformation of Theileria parva infected lymphocytes

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Title: MDM2 regulates a novel form of incomplete neoplastic transformation of Theileria parva infected lymphocytes
Authors: Hayashida, Kyoko Browse this author
Kajino, Kiichi Browse this author →KAKEN DB
Hattori, Masakazu Browse this author
Wallace, Maura Browse this author
Morrison, Ivan Browse this author
Greene, Mark I. Browse this author
Sugimoto, Chihiro Browse this author →KAKEN DB
Keywords: Lymhoproliferation
Theileria parva
MDM2
p53
Issue Date: Feb-2013
Publisher: Elsevier
Journal Title: Experimental and Molecular Pathology
Volume: 94
Issue: 1
Start Page: 228
End Page: 238
Publisher DOI: 10.1016/j.yexmp.2012.08.008
PMID: 22981919
Abstract: Our efforts are concerned with identifying features of incomplete malignant transformation caused by non viral pathogens. Theileria parva (T. parva) is a tick-transmitted protozoan parasite that can cause a fatal lymphoproliferative disease in cattle. The T. parva-infected lymphocytes display a transformed phenotype and proliferate in culture media like the other tumor cells, however those cells will return to normal after antiprotozoal treatment reflecting the incomplete nature of transformation. To identify signaling pathways involved in this form of transformation of T. parva-infected cells, we screened a library of anticancer compounds. Among these, TIBC, a specific inhibitor of MDM2, markedly inhibited proliferation of T. parva-infected lymphocytes and promoted apoptosis. Therefore we analyzed MDM2 function in T. parva-infected cells. Several T. parva-infected cell lines showed increased expression level of MDM2 with alternatively spliced isoforms compared to the lymphoma cells or ConA blasts. In addition, buparvaquone affected MDM2 expression in T. parva transformed cells. Moreover, p53 protein accumulation and function were impaired in T. parva-infected cells after cisplatin induced DNA damage despite the increased p53 transcription level. Finally, the treatment of T. parva-infected cells with boronic-chalcone derivatives TIBC restored p53 protein accumulation and induced Bax expression. These results suggest that the overexpression of MDM2 is closely linked to the inhibition of p53-dependent apoptosis of T. parva-infected lymphocytes. Aberrant expression of host lymphocyte MDM2 induced by cytoplasmic existence of T. parva, directly and/or indirectly, is associated with aspects of this type of transformation of T. parva-infected lymphocytes. This form of transformation shares features of oncogene induced malignant phenotype acquisition.
Type: article (author version)
URI: http://hdl.handle.net/2115/52236
Appears in Collections:人獣共通感染症リサーチセンター (Research Center for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 林田 京子

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