title: Localization of PKCη in cell membranes as a predictor for breast cancer response to treatment.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel.
authors.forename: Galia
authors.initials: G
authors.lastname: Karp
authors.forename: Sara
authors.initials: S
authors.lastname: Abu-Ghanem
authors.forename: Victor
authors.initials: V
authors.lastname: Novack
authors.forename: Wilmosh
authors.initials: W
authors.lastname: Mermershtain
authors.forename: Samuel
authors.initials: S
authors.lastname: Ariad
authors.forename: Netta
authors.initials: N
authors.lastname: Sion-Vardy
authors.forename: Etta
authors.initials: E
authors.lastname: Livneh
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D011493:Protein Kinase C / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D004317:Doxorubicin; D003520:Cyclophosphamide; C081975:protein kinase C eta; D011493:Protein Kinase C; D005472:Fluorouracil