Defined factors induce reprogramming of gastrointestinal cancer cells

• Norikatsu Miyoshi

  Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; and

• Hideshi Ishii

  Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; and

• Ken-ichi Nagai

  Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; and

• Hiromitsu Hoshino

  Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; and

• Koshi Mimori

  Department of Molecular and Cellular Biology, Division of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Ohita 874-0838, Japan

• Fumiaki Tanaka

  Department of Molecular and Cellular Biology, Division of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Ohita 874-0838, Japan

• Hiroaki Nagano

  Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; and

• Mitsugu Sekimoto

  Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; and

• Yuichiro Doki

  Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; and

• Masaki Mori

  Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan; and

抄録

Although cancer is a disease with genetic and epigenetic origins, the possible effects of reprogramming by defined factors remain to be fully understood. We studied the effects of the induction or inhibition of cancer-related genes and immature status-related genes whose alterations have been reported in gastrointestinal cancer cells. Retroviral-mediated introduction of induced pluripotent stem (iPS) cell genes was necessary for inducing the expression of immature status-related proteins, including Nanog, Ssea4, Tra-1-60, and Tra-1-80 in esophageal, stomach, colorectal, liver, pancreatic, and cholangiocellular cancer cells. Induced cells, but not parental cells, possessed the potential to express morphological patterns of ectoderm, mesoderm, and endoderm, which was supported by epigenetic studies, indicating methylation of DNA strands and the histone H3 protein at lysine 4 in promoter regions of pluripotency-associated genes such as NANOG . In in vitro analysis induced cells showed slow proliferation and were sensitized to differentiation-inducing treatment, and in vivo tumorigenesis was reduced in NOD/SCID mice. This study demonstrated that pluripotency was manifested in induced cells, and that the induced pluripotent cancer (iPC) cells were distinct from natural cancer cells with regard to their sensitivity to differentiation-inducing treatment. Retroviral-mediated introduction of iPC cells confers higher sensitivity to chemotherapeutic agents and differentiation-inducing treatment.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 107 (1), 40-45, 2009-12-29

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1360565167084142976
• NII論文ID: 80020947826
• DOI: 10.1073/pnas.0912407107
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.0912407107
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