PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression

Ryutaro Uchi, R. Kogo, K. Kawahara, T. Sudo, T. Yokobori, H. Eguchi, K. Sugimachi, T. Maehama, Masaki Mori, A. Suzuki, S. Komune, K. Mimori

研究成果: ジャーナルへの寄稿学術誌査読

24 被引用数 (Scopus)

抄録

Background:The TP53 pathway is frequently inactivated in human cancers. PICT1 (also known as GLTSCR2) is a novel regulator of the MDM2-TP53 pathway via its interaction with the ribosomal protein RPL11 in the nucleolus. However, the clinical significance of PICT1 in gastric cancer remains unknown.Methods:To evaluate PICT1 function, we used shRNA to inhibit PICT1 expression in gastric cancer cells that expressed wild-type TP53. PICT1 expression and TP53 mutation status were quantified in 110 cases of primary gastric cancer to explore the impact of PICT1 expression levels on gastric cancer.Results:Deficiency of PICT1 significantly impaired cell proliferation and colony formation via TP53-mediated cell cycle arrest. Following induction of PICT1 deficiency, RPL11 translocated out of the nucleolus. Of the 110 gastric cancer samples tested, 70 (63.6%) and 40 (36.4%) tumours expressed wild-type and mutant TP53, respectively. In gastric cancer patients with wild-type TP53 tumours, patients with relatively low PICT1 expression levels had a better prognosis compared with high expression level patients (P=0.046).Conclusion:The findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. Clinically, PICT1 expression is a novel prognostic parameter in gastric cancer patients with wild-type TP53 tumours.

本文言語英語
ページ(範囲)2199-2206
ページ数8
ジャーナルBritish journal of cancer
109
8
DOI
出版ステータス出版済み - 10月 15 2013

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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