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Research Paper
PKCη Expression Contributes to the Resistance of Hodgkin's Lymphoma Cell Lines to Apoptosis
Sara Abu-Ghanem, Galia Oberkovitz, Daniel Benharroch, Jacob Gopas and Etta Livneh
volume 6 | issue 9
September 2007Pages: 1375 - 1380
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The Hodgkin-Reed-Sternberg (HRS) malignant cells in Hodgkin's lymphoma (HL) originate from germinal center B lymphocytes that did not undergo apoptosis. Protein Kinase C (PKC), a family of serine/threonine kinases, plays a crucial role in signal transduction modulating cell growth, differentiation and apoptosis. Here, we report the expression of PKC isoforms in two HL-derived cell lines, L428 and KMH2 and their correlation with drug resistance to CPT and doxorubicin. Among the PKC isoforms examined, only PKCη and PKCβΙΙ were preferentially expressed in the drug resistant L428 cells. We have shown correlation between the response to apoptosis of L428 and KMH2 cells and PKCη expression in these cell lines. In order to directly demonstrate a role for PKCη in apoptosis, its expression was knocked-down by siRNA in the resistant L428 cells. Down-regulation of PKCη rendered L428 cells more sensitive to doxorubicin and CPT. Furthermore, PKCη knocked-down cells showed increased PARP-1 cleavage, cytochrome c release and caspase 7 activation. It appears that PKCη functions as an anti-apoptotic protein in HL-derived cell lines, and as we show here that it is also expressed in HRS of HL biopsies, it may have therapeutic relevance in HL. Thus, PKCη could provide a new target aimed to reduce resistance to anti-cancer treatments of HL and other cancer patients.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.