Translational Therapeutics

British Journal of Cancer (2009) 101, 256–262. doi:10.1038/sj.bjc.6605166 www.bjcancer.com
Published online 30 June 2009

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

T Zaremba1, P Ketzer2, M Cole1, S Coulthard1, E R Plummer1 and N J Curtin1

  1. 1Northern Institute for Cancer Research, Newcastle University, Paul O'Gorman Building, Newcastle upon Tyne NE2 4HH, UK
  2. 2Department of Biology, University of Konstanz, Konstanz 78457, Germany

Correspondence: Professor NJ Curtin, E-mail: n.j.curtin@ncl.ac.uk

Revised 7 May 2009; Accepted 3 June 2009; Published online 30 June 2009.

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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/106 (HS-5 cells) and 85 750 pmol PAR/106 (NGP cells). Lower variation (CV=32%) was observed in PARP-1 protein expression with the lowest expression being 2.0 ng mug-1 (HS-5 cells) and the highest being 7.1 ng mug-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.

Keywords:

PARP, PARP activity, PARP expression, polymorphisms, cancer cell lines