PKCη expression contributes to the resistance of Hodgkin's lymphoma cell lines to apoptosis

Sara Abu-Ghanem, Galia Oberkovitz, Daniel Benharroch, Jacob Gopas, Etta Livneh

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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 PKCβII 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. Downregulation of PKCh 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.

Original languageEnglish
Pages (from-to)1371-1376
Number of pages6
JournalCancer Biology and Therapy
Volume6
Issue number9
DOIs
StatePublished - 1 Jan 2007

Keywords

  • Apoptosis
  • Camptothecin
  • Doxorubicin
  • Hodgkin's lymphoma
  • PKCη

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