Hypoxia and TP53 deficiency for induced pluripotent stem cell-like properties in gastrointestinal cancer

Hiromitsu Hoshino, Hiroaki Nagano, Naotsugu Haraguchi, Shimpei Nishikawa, Akira Tomokuni, Yoshihiro Kano, Takahito Fukusumi, Toshiyuki Saito, Miyuki Ozaki, Daisuke Sakai, Taroh Satoh, Hidetoshi Eguchi, Mitsugu Sekimoto, Yuichiro Doki, Masaki Mori, Hideshi Ishii

研究成果: Contribution to journalArticle査読

10 被引用数 (Scopus)

抄録

Induced pluripotent stem (iPS)-like cancer cells (iPC) by the introduction of defined transcription factors reduce the prevalence of the malignant phenotype of digestive system cancer cells, but the induction efficiency is low. The role of hypoxia and TP53 deficiency in iPC cell generation remain unclear. Cellular reprogramming was performed by retroviral infection with OCT3/4, SOX2, KLF4 and c-MYC of wild-type HCT116 colorectal cancer cells and mutant TP53-deficient HCT116 cells. Cells were cultured in normoxia (21% O 2) or hypoxia (5% O 2) for 30 days after transduction, and the response to hypoxia and comparison of cellular proliferation, invasion and tumourigenesis before and after iPC cell generation were studied. iPC cell generation from wild-type HCT116 cells in hypoxia was approximately 4-times greater than in normoxia (p<0.05), and TP53 deficiency increased conversion efficiency significantly in normoxia (p<0.05). Significant involvement of hypoxia-inducible factors was observed in an immature carbohydrate epitope, Tra-1-60 +, colony formation. Generated iPC cells exhibited multi-differentiation potential. Although the iPC cells in hypoxia exhibited reduced proliferation, invasiveness and tumourigenicity, TP53 deficiency in iPC cells resulted in higher tumourigenicity than in wild-type cells. Both hypoxia and TP53 deficiency increase iPC cell generation. TP53 deficiency can also result in deleterious mutations, whereas hypoxia may impact molecular targets of epigenome normalisation.

本文言語英語
ページ(範囲)1423-1430
ページ数8
ジャーナルInternational journal of oncology
40
5
DOI
出版ステータス出版済み - 5 2012

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

フィンガープリント 「Hypoxia and TP53 deficiency for induced pluripotent stem cell-like properties in gastrointestinal cancer」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル