Absence of specific cell killing of the BRCA2-deficient human cancer cell line CAPAN1 by poly(ADP-ribose) polymerase inhibition

被引:49
作者
Gallmeier, E
Kern, SE
机构
[1] Johns Hopkins Univ, Dept Oncol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA
[2] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA
关键词
BRCA2; breast cancer; CAPAN1; pancreatic cancer; PARP inhibition; poly(ADP-ribose) polymerase; selective cell killing;
D O I
10.4161/cbt.4.7.1909
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:703 / 706
页数:4
相关论文
共 17 条
[1]   BRCA2 regulates homologous recombination in response to DNA damage: Implications for genome stability and carcinogenesis [J].
Abaji, C ;
Cousineau, I ;
Belmaaza, A .
CANCER RESEARCH, 2005, 65 (10) :4117-4125
[2]   Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase [J].
Bryant, HE ;
Schultz, N ;
Thomas, HD ;
Parker, KM ;
Flower, D ;
Lopez, E ;
Kyle, S ;
Meuth, M ;
Curtin, NJ ;
Helleday, T .
NATURE, 2005, 434 (7035) :913-917
[3]   The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment [J].
Chen, PL ;
Chen, CF ;
Chen, YM ;
Xiao, J ;
Sharp, ZD ;
Lee, WH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (09) :5287-5292
[4]   Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy [J].
Farmer, H ;
McCabe, N ;
Lord, CJ ;
Tutt, ANJ ;
Johnson, DA ;
Richardson, TB ;
Santarosa, M ;
Dillon, KJ ;
Hickson, I ;
Knights, C ;
Martin, NMB ;
Jackson, SP ;
Smith, GCM ;
Ashworth, A .
NATURE, 2005, 434 (7035) :917-921
[5]  
Goggins M, 1996, CANCER RES, V56, P5360
[6]   Resistance-modifying agents. 5. Synthesis and biological properties of quinazolinone inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) [J].
Griffin, RJ ;
Srinivasan, S ;
Bowman, K ;
Calvert, AH ;
Curtin, NJ ;
Newell, DR ;
Pemberton, LC ;
Golding, BT .
JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (26) :5247-5256
[7]   Large-scale allelotype of pancreaticobiliary carcinoma provides quantitative estimates of genome-wide allelic loss [J].
Iacobuzio-Donahue, CA ;
van der Heijden, MS ;
Baumgartner, MR ;
Troup, WJ ;
Romm, JM ;
Doheny, K ;
Pugh, E ;
Yeo, CJ ;
Goggins, MG ;
Hruban, RH ;
Kern, SE .
CANCER RESEARCH, 2004, 64 (03) :871-875
[8]   Homologous repair of DNA damage and tumorigenesis: the BRCA connection [J].
Jasin, M .
ONCOGENE, 2002, 21 (58) :8981-8993
[9]   Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2 [J].
King, MC ;
Marks, JH ;
Mandell, JB .
SCIENCE, 2003, 302 (5645) :643-646
[10]   BRCA2 is required for homology-directed repair of chromosomal breaks [J].
Moynahan, ME ;
Pierce, AJ ;
Jasin, M .
MOLECULAR CELL, 2001, 7 (02) :263-272