Localization of PKCη in cell membranes as a predictor for breast cancer response to treatment

Galia Karp, Sara Abu-Ghanem, Victor Novack, Wilmosh Mermershtain, Samuel Ariad, Netta Sion-Vardy, Etta Livneh

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background: Successful treatment of breast cancer is frequently limited by the resistance of tumors to chemotherapy. Recent studies suggested a role for protein kinase C (PKC) in the resistance to chemotherapy. Here we used retrospective analysis of breast cancer biopsies of neoadjuvantly treated patients to investigate the correlation of PKC expression with aggressiveness and resistance to chemotherapy. Patients and Methods: Our cohort (n = 25) included patients with advanced and aggressive breast cancers, who underwent neoadjuvant therapy with the CAF regimen (cyclophosphamide, doxorubicin, fluorouracil). Core biopsies (pre-chemotherapy) and surgical biopsies of primary tumors and lymph node metastases (post-chemotherapy) were scored for PKCeta (PKCh) and PKCepsilon (PKCe) expression in the cytoplasm, cell membrane, nuclear membrane, and the nucleus. Results: Our results showed increased expression of PKCh (not PKCe) in the cytoplasm and cell membranes of post-chemotherapy biopsies (p = 0.03). PKCh presence in cell membranes, indicating activation, was in correlation with poor survival (p = 0.007). Conclusion: PKCh staining in cell and nuclear membranes is an indicator for poor survival and a predictor for the effectiveness of neoadjuvant treatment. Other avenues of treatment should be considered for these patients. PKCh presents a target for therapy where inhibition of its activity and/or translocation to membranes could interfere with the resistance to chemotherapy.

Original languageEnglish
Pages (from-to)260-266
Number of pages7
JournalOnkologie
Volume35
Issue number5
DOIs
StatePublished - 1 May 2012

Keywords

  • Apoptosis
  • Breast cancer
  • Neoadjuvant
  • PKCh
  • Predicting response to therapy

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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