Poly(ADP-ribose) polymerase-1 polymorphisms, expression and activity in selected human tumour cell lines

• Published in: British journal of cancer 2009-07, Vol.101 (2), p.256-262
• Main Authors: Zaremba, T, Ketzer, P, Cole, M, Coulthard, S, Plummer, E R, Curtin, N J
• Format: Article
• Language: English
• Subjects: Binding sites; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Line, Tumor; DNA repair; Drug Resistance; Enzymes; Epidemiology; Humans; Liver cancer; Lymphocytes - enzymology; Medical research; Microsatellite Repeats; Molecular Medicine; Neoplasms - enzymology; Neoplasms - genetics; Oncology; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - biosynthesis; Poly(ADP-ribose) Polymerases - genetics; Poly(ADP-ribose) Polymerases - metabolism; Polymorphism; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Protein expression; Proteins; Transcription factors; Translational Therapeutics
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605166

Background: Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA-binding enzyme activated by DNA breaks and involved in DNA repair and other cellular processes. Poly(ADP-ribose) polymerase activity can be higher in cancer than in adjacent normal tissue, but cancer predisposition is reported to be greater in individuals with a single-nucleotide polymorphism (SNP) V762A (T2444C) in the catalytic domain that reduces PARP-1 activity. Methods: To resolve these divergent observations, we determined PARP-1 polymorphisms, PARP-1 protein expression and activity in a panel of 19 solid and haematological, adult and paediatric human cancer cell lines. Results: There was a wide variation in PARP activity in the cell line panel (coefficient of variation, CV=103%), with the lowest and the highest activity being 2460 pmol PAR/10 6 (HS-5 cells) and 85 750 pmol PAR/10 6 (NGP cells). Lower variation (CV=32%) was observed in PARP-1 protein expression with the lowest expression being 2.0 ng  μ g −1 (HS-5 cells) and the highest being 7.1 ng  μ g −1 (ML-1 cells). The mean activity in the cancer cells was 45-fold higher than the mean activity in normal human lymphocytes and the PARP-1 protein levels were 23-fold higher. Conclusions: Surprisingly, there was no significant correlation between PARP activity and PARP-1 protein level or the investigated polymorphisms, T2444C and CA.