Analysis of novel tumor suppressor gene RUNX3 in gastric cancer

• Project/Area Number: 17390374
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyoto prefectural University of Medicine
• Principal Investigator: SAKAKURA Chouhei Kyoto Prefectural University of Medicine, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (10285257)
• Co-Investigator(Kenkyū-buntansha): HAGIWARA Akeo Kyoto Prefectural University of Medicine, Graduate School of Medicine, Associate professor, 医学研究科, 准教授 (90198648) ; OKUDA Tsukasa Kyoto Prefectural University of Medicine, Graduate School of Medicine, Associate professor, 医学研究科, 准教授 (30291587) ; CHIBA Tsutomu Kyoto University, Graduate School of Medicine, professor, 医学研究科, 教授 (30188487)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥7,400,000 (Direct Cost: ¥7,400,000); Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000); Fiscal Year 2005: ¥4,700,000 (Direct Cost: ¥4,700,000)
• Keywords: Gastric cancer / RUNX3 / Suppressor gene

Research Abstract

The human runt-related gene RUNX3, located on chromosome 1p36, is a major mediator of signals elicited by members of the transforming growth factor-β (TGF-β) superfamily. Here we show that 45-60% of gastric cancer cell lines and surgically resected specimens do not significantly express RUNX3 due to a combination of hemizygous deletion and hypermethylation of the RUNX3 promoter region. Tumorigenicity of gastric cancer cell lines in nude mice was inversely related to their level of AML2(RUNX3) expression, and one gastric tumor associated mutation (R122C), occurring within the conserved Runt domain completely abolished the tumor suppressive effect of RUNX3. The results suggest that a lack of RUNX3 function is causally related to the genesis and progression of human gastric cancer.

Research Products

• [Journal Article] Endocrine Cell and Nerve Regeneration in Autologous In Situ Tissue-Engineered Small Intestine. (2007)
  • Author(s): Nakase Y, Nakamura T, Kin S, Nakashima S, Yoshikawa T, Kuriu Y, Miyagawa K, Sakakura C, Otsuji E, Ikada Y, Yamagishi H, Hagiwara A.
  • Journal Title: J Surg Res., Epub 2006 Nov3 137(1) Pages: 61-68
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Down-regulation of RUNX1, RUNX3 and CBFbeta in hepatocellular carcinomas in an early stage of hepatocarcinogenesis. (2006)
  • Author(s): Miyagawa K, Sakakura C, et al.
  • Journal Title: Anticancer Res 26(5B) Pages: 3633-3643
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Long-term survival of a case with multiple liver metastases from duodenal gastrointestinal stromal tumor drastically reduced by the treatment with imatinib and hepatectomy (2006)
  • Author(s): Sakakura C, et al.
  • Journal Title: World J Gastroentero 12 Pages: 2793-2797
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genomic loss and epigenetic silencing of very-low-density lipoprotein receptor involved in gastric carcinogenesis. (2006)
  • Author(s): Takada H, Imoto I, Tsuda H, Nakanishi Y, Sakakura C, Mitsufuji S, Hirohashi S, Inazawa J
  • Journal Title: Oncogene
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Endocrine cell and nerve regeneration in autologous in situtissue-engineered small intestine. (2006)
  • Author(s): Nakase Y, Nakamura T, Kin S, Nakashima S, Yoshikawa T, Kurou Y, Miyagawa K, Sakakura C, Otsuji E, Ikada Y, Yamagishi H, Hagiwara A
  • Journal Title: J Surg Res. 137(1) Pages: 61-68
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Tissue engineering of small intestinal tissue using collagen sponge scaffolds seeded with smooth muscle cells. (2006)
  • Author(s): Nakase Y, Hagiwara A, Nakamura T, Kin S, Nakashima S, Yoshikawa T, Fukuda K, Kuriu Y, Miyagawa K, Sakakura C, Otsuji E, Shimizu Y, Ikada Y, Yamagishi H
  • Journal Title: Tissue Eng 12 Pages: 403-412
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Down-regulation of RUNX1, RUNX3 and CBFbeta in hepatocellular carcinomas in an early stage of hepatocarcinogenesis. (2006)
  • Author(s): Miyagawa K, Sakakura C, Nakashima S, Yoshikawa T, Kin S, Nakase Y, Ito K, Yamagishi H, Ida H, Yazumi S, Chiba T, Ito Y, Hagiwara A.
  • Journal Title: Anticancer Res. 26(5B) Pages: 3633-43
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Long-term survival of a case with multiple liver metastases from duodenal gastrointestinal stromal tumor drastically reduced by the treatment with imatinib and hepatectomy. (2006)
  • Author(s): Sakakura C, Hagiwara A, Soga K, Miyagawa K, Nakashima S, Yoshikawa T, Kin S, Nakase Y, Yamaoka N, Sagara Y, Yamagishi H.
  • Journal Title: World J Gastroenterol. 12(17) Pages: 2793-7
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genomic loss and epigenetic silencing of very-low-density lipoprotein receptor involved in gastric carcinogenesis. (2006)
  • Author(s): Takada H, Imoto I, Tsuda H, Nakanishi Y, Sakakura C, Mitsufuji S, Hirohashi S, Inazawa J.
  • Journal Title: Oncogene., Epub 2006 May22 25(49) Pages: 6554-62
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Tissue engineering of small intestinal tissue using collagen sponge scaffolds seeded with smooth muscle cells. (2006)
  • Author(s): Nakase Y, Hagiwara A, Nakamura T, Kin S, Nakashima S, Yoshikawa T, Fukuda K, Kuriu Y, Miyagawa K, Sakakura C, Otsuji E, Shimizu Y, Ikada Y, Yamagishi H.
  • Journal Title: Tissue Eng 12(2) Pages: 403-12
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] down-regulation of RUNX1, RUNX3 and CBFbeta in hepatocellular carcinomas in an early stage of hepatocarcinogenesis. (2006)
  • Author(s): Miyagawa K, Sakakura C, et al.
  • Journal Title: Anticancer Res 26(5B) Pages: 3633-3643
• [Journal Article] Genomic loss and epigenetic silencing of very-low-density lipoprotein receptor involved in gastric carcinogenesis. (2006)
  • Author(s): Takada H, Imoto I, Tsuda H, Nakanishi Y, Sakakura C, Mitsufuji S, Hirohashi S, Inazawa J.
  • Journal Title: Oncogene 25 Pages: 6554-62
• [Journal Article] Long-tem survival of a case with multiple liver metastases from duodenal gastrointestinal stromal tumor drastically reduced by the treatment with imatinib and hepatectomy (2006)
  • Author(s): Sakakura C, et al.
  • Journal Title: World J Gastroentero 12
• [Journal Article] Endocrine cell and nerve regeneration in autologous in situ tissue-engineered small intestine. (2006)
  • Author(s): Nakase Y, Nakamura T, Kin S, Nakashima S, Yoshikawa T, Kurou Y, Miyagawa K, Sakakura C, Otsuji E, Ikada Y, Yamagishi H, Hagiwara A.
  • Journal Title: J Surg Res. 137(1): Pages: 61-68
• [Journal Article] Tissue engineering of small intestinal tissue using collagen sponge scaffolds seeded with smooth muscle cells. (2006)
  • Author(s): Nakase Y, Hagiwara A, Nakamura T, Kin S, Nakashima S, Yoshikawa T, Fukuda K, Kuriu Y, Miyagawa K, Sakakura C, Otsuji E, Shimizu Y, Ikada Y, Yamagishi H.
  • Journal Title: Tissue Eng 12 Pages: 403-412
• [Journal Article] Frequent downregulation of the runt domain transcription factors RUNX1, RUNX3 and their cofactor CBFB in gastric cancer (2005)
  • Author(s): Sakakura C, et al.
  • Journal Title: Int J Cancer 113(2) Pages: 221-228
• [Journal Article] Possible involvement of RUNX3 silencing in the peritoneal metastases of gastric cancers (2005)
  • Author(s): Sakakura C, et al.
  • Journal Title: Clin Cancer Res. 11(18) Pages: 6479-6488
• [Journal Article] Frequent loss of RUNX3 gene expression in remnant stomach cancer and adjacent mucosa with special reference to topography. (2005)
  • Author(s): Nakase Y, Sakakura C et al.
  • Journal Title: Br J Cancer 113(2) Pages: 221-228
• [Journal Article] RUNX3 suppresses gastric epithelial cell growth by inducing p21(WAF1/Cip1) expression in cooperation with transforming growth factor {beta}-activated SMAD. (2005)
  • Author(s): Chi XZ, Yang JO, Lee KY, Ito K, Sakakura C, et al.
  • Journal Title: Mol Cell Biol 25(18): Pages: 8097-8107