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

Hayashida, Kyoko; Kajino, Kiichi; Hattori, Masakazu; Wallace, Maura; Morrison, Ivan; Greene, Mark I.; Sugimoto, Chihiro

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

Hayashida, Kyoko; Kajino, Kiichi; Hattori, Masakazu et al.

Experimental and Molecular Pathology, 2013, 94(1), 228-238

Permalink : https://hdl.handle.net/2115/52236

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アクセス権	open access
URI	https://hdl.handle.net/2115/52236
タイトル	MDM2 regulates a novel form of incomplete neoplastic transformation of Theileria parva infected lymphocytes
著者	Hayashida, Kyoko ; Kajino, Kiichi ; Hattori, Masakazu ; Wallace, Maura ; Morrison, Ivan ; Greene, Mark I. ; Sugimoto, Chihiro
著者名 Hayashida, Kyoko
e-Rad_Researcher 80322147 著者名 Kajino, Kiichi
著者名 Hattori, Masakazu
著者名 Wallace, Maura
著者名 Morrison, Ivan
著者名 Greene, Mark I.
e-Rad_Researcher 90231373 著者名 Sugimoto, Chihiro
言語	英語
キーワード	Lymhoproliferation
	Theileria parva
	MDM2
	p53
発行日	2013-02
出版者	Elsevier
収録物名	Experimental and Molecular Pathology
巻(号)	94(1)
ページ	228-238
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0014-4800
関連情報	PMID 22981919
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.yexmp.2012.08.008