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

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)8-15
Number of pages8
JournalCancer Genetics and Cytogenetics
Volume197
Issue number1
DOIs
Publication statusPublished - 2010 Feb
Externally publishedYes

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Germ Cell and Embryonal Neoplasms
Tumor Cell Line
Genes
Amino Acid Substitution
Proteins
Single Nucleotide Polymorphism
Alleles
Poly (ADP-Ribose) Polymerase-1
Genomic Instability
DNA Repair
Adenosine Diphosphate
Healthy Volunteers
Cell Death
Radiotherapy
Maintenance
Drug Therapy
Cell Line
Peptides

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Analysis of poly(ADP-ribose) polymerase-1 (PARP1) gene alteration in human germ cell tumor cell lines. / Ogino, Hideki; Nakayama, Turrent Robert; Sakamoto, Hiromi; Yoshida, Teruhiko; Sugimura, Takashi; Masutani, Mitsuko.

In: Cancer Genetics and Cytogenetics, Vol. 197, No. 1, 02.2010, p. 8-15.

Research output: Contribution to journalArticle

Ogino, Hideki ; Nakayama, Turrent Robert ; Sakamoto, Hiromi ; Yoshida, Teruhiko ; Sugimura, Takashi ; Masutani, Mitsuko. / Analysis of poly(ADP-ribose) polymerase-1 (PARP1) gene alteration in human germ cell tumor cell lines. In: Cancer Genetics and Cytogenetics. 2010 ; Vol. 197, No. 1. pp. 8-15.
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