کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5888278 1152309 2013 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
MDM2 regulates a novel form of incomplete neoplastic transformation of Theileria parva infected lymphocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی بالینی
پیش نمایش صفحه اول مقاله
MDM2 regulates a novel form of incomplete neoplastic transformation of Theileria parva infected lymphocytes
چکیده انگلیسی

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.

► The MDM2 inhibitor TIBC promoted apoptosis of T. parva-infected lymphocytes. ► Increased expressions of MDM2 with alternatively spliced isoforms were observed. ► p53 response to DNA damage was disordered in T. parva-infected lymphocytes. ► We document a mechanism of parasite-induced incomplete transformation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental and Molecular Pathology - Volume 94, Issue 1, February 2013, Pages 228-238
نویسندگان
, , , , , , ,