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

Lookup NU author(s): Tomasz Zaremba, Mike Cole, Dr Sally Coulthard, Professor Ruth Plummer, Professor Nicola Curtin

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Abstract

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 mu g(-1) (HS-5 cells) and the highest being 7.1 ng mu 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. British Journal of Cancer (2009) 101, 256-262. doi:10.1038/sj.bjc.6605166 www.bjcancer.com Published online 30 June 2009 (C) 2009 Cancer Research UK


Publication metadata

Author(s): Zaremba T, Ketzer P, Cole M, Coulthard S, Plummer ER, Curtin NJ

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2009

Volume: 101

Issue: 2

Pages: 256-262

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/sj.bjc.6605166

DOI: 10.1038/sj.bjc.6605166


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