Absence of specific cell killing of the BRCA2-deficient human cancer cell line CAPAN1 by poly(ADP-ribose) polymerase inhibition.
The specific killing of cells impaired in BRCA2 function upon treatment with poly (ADP-ribose) polymerase (PARP) inhibitors has recently been reported by two groups. CAPAN1, which was not characterized in these reports, represents the only human cancer cell line harboring the frequent, naturally occurring BRCA2 6174delT frameshift mutation accompanied by loss of the second allele. The severe impact of this mutation on BRCA2 function has been extensively characterized. However, PARP inhibition by 3-aminobenzamide or NU1025 did not result in significant cell death in CAPAN1 cells. Our data raise concern about the uniformity of the specific cell killing of BRCA2-deficient cells upon PARP inhibition and therefore urge caution as to whether prior findings are fully generalizable for the specific treatment of human cancers harboring naturally occurring, inactivating forms of BRCA2 mutations.
Gallmeier
Eike
E
Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Baltimore, Maryland, USA.
Kern
Scott E
SE
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D024682:BRCA2 Protein / Q000172:deficiency* / Q000235:genetics; D001549:Benzamides / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016368:Frameshift Mutation; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011799:Quinazolines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D024682:BRCA2 Protein; D001549:Benzamides; D004791:Enzyme Inhibitors; C115774:NU 1025; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011799:Quinazolines; C025160:3-aminobenzamide