Dominant-negative mutations of the tumor suppressor p53 relating to early onset of glioblastoma multiforme

Masumi Marutani, Hidefumi Tonoki, Mitsuhiro Tada, Masato Takahashi, Haruhiko Kashiwazaki, Yasuhiro Hida, Jun Ich Hamada, Masahiro Asaka, Tetsuya Moriuchi

研究成果: Contribution to journalArticle査読

59 被引用数 (Scopus)

抄録

Previous experiments have suggested that some mutant forms of p53 are able to inactivate the endogenous wild-type p53 protein in a dominantnegative fashion. However, it remains unknown whether tumors with such dominant- negative (transdominant) p53 mutants have a biological significance that is different from that of recessive p53 mutants. In this study, we examined the dominant-negative potential of various p53 mutants using a yeast-based assay in which both wild-type and mutant p53 were efficiently expressed. We tested a total of 106 p53 mutants, which were identified in brain tumors, glioblastoma multiforme-derived cell lines, breast cancers, or premalignant lesions and squamous cell carcinomas of oral epithelium or were otherwise created by mutagenesis. In agreement with the previous studies, our results demonstrated that transdominant mutations affected amino acid residues that are essential for the stabilization of the DNA-binding surface in the p53 core domain and for the direct interaction of p53 with its DNA-binding sequence. Among 40 patients with sporadic glioblastomas, the average age at diagnosis was significantly younger in the patients with tumors harboring dominantnegative mutations (30.4 ± 14.7 years, n = 7) than it was in those with recessive mutations (55.2 ± 18.6 years, n = 9, P < 0.012) and in those without mutations (54.7 ± 17.1 years, n = 24, P < 0.003). Our data suggest that dominant-negative p53 mutants accelerate development and/or growth of glioblastoma anlagen.

本文言語英語
ページ(範囲)4765-4769
ページ数5
ジャーナルCancer Research
59
19
出版ステータス出版済み - 10 1 1999
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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