Poly(ADP-ribose) polymerase-1 polymorphisms, expression and activity in selected human tumour cell lines.
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 microg(-1) (HS-5 cells) and the highest being 7.1 ng microg(-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.
Zaremba
T
T
Northern Institute for Cancer Research, Newcastle University, Paul O'Gorman Building, Newcastle upon Tyne NE2 4HH, UK.
Ketzer
P
P
Cole
M
M
Coulthard
S
S
Plummer
E R
ER
Curtin
N J
NJ
D045744:Cell Line, Tumor; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D018895:Microsatellite Repeats; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases