Analysis of poly(ADP-ribose) polymerase-1 (PARP1) gene alteration in human germ cell tumor cell lines

Hideki Ogino, Robert Nakayama, Hiromi Sakamoto, Teruhiko Yoshida, Takashi Sugimura, Mitsuko Masutani

研究成果: Article査読

8 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)8-15
ページ数8
ジャーナルCancer Genetics and Cytogenetics
197
1
DOI
出版ステータスPublished - 2010 2月
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 遺伝学
  • 癌研究

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