TY - JOUR
T1 - Analysis of poly(ADP-ribose) polymerase-1 (PARP1) gene alteration in human germ cell tumor cell lines
AU - Ogino, Hideki
AU - Nakayama, Robert
AU - Sakamoto, Hiromi
AU - Yoshida, Teruhiko
AU - Sugimura, Takashi
AU - Masutani, Mitsuko
N1 - Funding Information:
We thank T. Otsubo, T. Okada, and S. Mimaki for technical help and suggestions. We are grateful for the kind support and suggestions of H. Nakagama. This work was supported in part by a Grant-in-Aid for the Second and Third Term Comprehensive 10-year Strategy for Cancer Control and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor, and Welfare of Japan.
PY - 2010/2
Y1 - 2010/2
N2 - The poly(ADP-ribose) polymerase-1 protein (PARP-1) functions in DNA repair, maintenance of genomic stability, induction of cell death, and transcriptional regulation. We previously analyzed alterations of the PARP1 gene in 16 specimens of human germ cell tumors, and found a heterozygous sequence alteration that causes the amino acid substitution Met129Thr (M129T) in both tumor and normal tissues in a single patient. In this study, aberration of the PARP1 gene and protein was further analyzed in human germ cell tumor cell lines. We found a nonheterozygous sequence alteration that causes the amino acid substitution Glu251Lys (E251K) located at a conserved peptide stretch of PARP-1 in cell line NEC8. Sequencing of 95 samples from Japanese healthy volunteers revealed that all the samples were homozygous for the wild-type alleles at M129T and E251K. The M129T allele is thus suggested to be a rare single-nucleotide polymorphism (SNP). We observed a decrease in auto-poly(ADP-ribosyl)ation activity of PARP-1 proteins harboring M129T or E251K amino acid substitution, but the difference was not statistically significant. The levels of PARP-1 and poly(ADP-ribosyl)ation were heterogeneous among germ cell tumor cell lines. The SNPs of the PARP1 gene, as well as differences in the levels of PARP-1 and poly(ADP-ribosyl)ation of proteins, may influence germ cell tumor development and responses to chemotherapy and radiotherapy.
AB - The poly(ADP-ribose) polymerase-1 protein (PARP-1) functions in DNA repair, maintenance of genomic stability, induction of cell death, and transcriptional regulation. We previously analyzed alterations of the PARP1 gene in 16 specimens of human germ cell tumors, and found a heterozygous sequence alteration that causes the amino acid substitution Met129Thr (M129T) in both tumor and normal tissues in a single patient. In this study, aberration of the PARP1 gene and protein was further analyzed in human germ cell tumor cell lines. We found a nonheterozygous sequence alteration that causes the amino acid substitution Glu251Lys (E251K) located at a conserved peptide stretch of PARP-1 in cell line NEC8. Sequencing of 95 samples from Japanese healthy volunteers revealed that all the samples were homozygous for the wild-type alleles at M129T and E251K. The M129T allele is thus suggested to be a rare single-nucleotide polymorphism (SNP). We observed a decrease in auto-poly(ADP-ribosyl)ation activity of PARP-1 proteins harboring M129T or E251K amino acid substitution, but the difference was not statistically significant. The levels of PARP-1 and poly(ADP-ribosyl)ation were heterogeneous among germ cell tumor cell lines. The SNPs of the PARP1 gene, as well as differences in the levels of PARP-1 and poly(ADP-ribosyl)ation of proteins, may influence germ cell tumor development and responses to chemotherapy and radiotherapy.
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U2 - 10.1016/j.cancergencyto.2009.10.012
DO - 10.1016/j.cancergencyto.2009.10.012
M3 - Article
C2 - 20113831
AN - SCOPUS:74749092324
SN - 0165-4608
VL - 197
SP - 8
EP - 15
JO - Cancer Genetics and Cytogenetics
JF - Cancer Genetics and Cytogenetics
IS - 1
ER -
