title: Expression of a novel peptide derived from PCNA damages DNA and reverses cisplatin resistance.
abstract: BACKGROUND
  An 8 amino acid peptide sequence derived from proliferating cell nuclear antigen (PCNA) has been shown to effectively kill several breast cancer and neuroblastoma cell lines when added exogenously to cell cultures.
  
  
  METHODS
  In this study, the expression of the 8 amino acid peptide sequence (caPeptide) was placed under control of a tetracycline responsive promoter in MDA-MB-231 cells.
  
  
  RESULTS
  Endogenous expression of the peptide resulted in an increase in genomic DNA damage. CaPeptide induction combined with treatment of sublethal doses of cisplatin resulted in a marked increase in death of the cisplatin-resistant MDA-MB-231 cell line. CaPeptide was found to interact with POLD3, one of the subunits of DNA polymerase delta necessary for binding to PCNA.
  
  
  CONCLUSIONS
  These results suggest an important line of inquiry into the possible role that caPeptide might play in the reversal of cisplatin resistance in breast and other cancers. This is of particular interest in those cancers where cisplatin is the first line of chemotherapy and where the acquisition of resistance is a common malady.
authors.affiliation: Department of Molecular Biology, Beckman Research Institute of the City of Hope, 1450 E. Duarte Rd., Duarte, CA, 91010, USA, rlingeman@coh.org.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Lingeman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hickey
authors.forename: Linda H
authors.initials: LH
authors.lastname: Malkas
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D004258:DNA Polymerase III / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D018809:Proliferating Cell Nuclear Antigen; D021122:Protein Subunits; C435720:POLD3 protein, human; D004258:DNA Polymerase III; D002945:Cisplatin