Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Growth regulation of gastric epithelial cells by Runx3

Oncogene volume 23, pages 4330–4335 (2004)Cite this article

Abstract

Runx3 is expressed by gastric epithelial cells throughout development. Mice whose Runx3 gene has been knocked out died soon after birth. In the knockout mouse, gastric epithelia exhibited hyperplasia and epithelial apoptosis was suppressed. Analysis using a primary culture system for the epithelial cells suggested that this is caused by the reduced sensitivity of Runx3−/− gastric epithelial cells to the growth-inhibiting and apoptosis-inducing activities of TGF-β. In human and mouse gastric cancer cell lines, RUNX3/Runx3 was silenced due to hypermethylation of CpG islands in the promoter region. Exogenous expression of RUNX3 in the cells that do not express the endogenous gene caused an inhibition of growth both in vivo and in vitro. These observations indicate that Runx3 is a major growth regulator of gastric epithelial cells, and that it is deeply involved in gastric tumorigenesis in both humans and mice.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Crawford SE, Stellmach V, Murphy-Ullrich JE, Ribeiro SM, Lawler J, Hynes RO, Boivin GP and Bouck N . (1998). Cell, 93, 1159–1170.

  • Furihata C, Tatematsu M, Saito M, Ishida S, Nakanishi H, Inada K, Tei H, Hattori M, Ito T and Sakaki Y . (1997). Jpn. J. Cancer Res., 88, 363–368.

  • Guo W-H, Weng L-Q, Ito K, Chen L-F, Nakanishi H, Tatematsu M and Ito Y . (2002). Oncogene, 21, 8351–8355.

  • Hanahan D and Weinberg RA . (2000). Cell, 100, 57–70.

  • Hanai J, Chen L-F, Kanno T, Ohtani-Fujita N, Kim W-Y, Guo W-H, Imamura T, Ishidou Y, Fukuchi M, Shi M-J, Stavnezer J, Kawabata M, Miyazono K and Ito Y . (1999). J. Biol. Chem., 274, 31577–31582.

  • Ichinose M, Nakanishi H, Fujino S and Tatematsu M . (1998). Jpn. J. Cancer Res., 89, 516–524.

  • Kallapur S, Ormsby I and Doetschman T . (1999). Mol. Reprod. Dev., 52, 341–349.

  • Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S and Kishimoto T . (1997). Cell, 89, 755–764.

  • Lee B, Thirunavukkarasu K, Zhou L, Pastore L, Baldini A, Hecht J, Geoffroy V, Ducy P and Karsenty G . (1997). Nat. Genet., 16, 307–310.

  • Levanon D, Bettoun D, Harris-Cerruti C, Woolf E, Negreanu V, Eilam R, Bernstein Y, Goldenberg D, Xiao C, Fliegauf M, Kremer E, Otto F, Brenner O, Lev-Tov A and Groner Y . (2002). EMBO J., 21, 3454–3463.

  • Levanon D, Brenner O, Otto F and Groner Y . (2003). EMBO Rep., 4, 560–564.

  • Li Q-L, Ito K, Sakakura C, Fukamachi H, Inoue K, Chi X-Z, Lee K-Y, Nomura S, Lee C-W, Han S-B, Kim H-M, Kim W-J, Yamamoto H, Yamashita N, Yano T, Ikeda T, Itohara S, Inazawa J, Abe T, Hagiwara A, Yamagishi H, Ooe A, Kaneda A, Sugimura T, Ushijima T, Bae S-C and Ito Y . (2002). Cell, 109, 113–124.

  • Linggi B, Muller-Tidow C, van de Locht L, Hu M, Nip J, Serve H, Berdel WE, van der Reijden B, Quelle DE, Rowley JD, Cleveland J, Jansen JH, Pandolfi PP and Hiebert SW . (2002). Nat. Med., 8, 743–750.

  • Look AT . (1997). Science, 278, 1059–1064.

  • Martikainen P, Kyprianou N and Isaacs JT . (1990). Endocrinology, 127, 2963–2968.

  • Mundlos S, Otto F, Mundlos C, Mulliken JB, Aylsworth AS, Albright S, Lindhout D, Cole WG, Henn W, Knoll JH, Owen MJ, Mertelsmann R, Zabel BU and Olsen BR . (1997). Cell, 89, 773–779.

  • Oberhammer FA, Pavelka M, Sharma S, Tiefenbacher R, Purchio AF, Bursch W and Schulte-Hermann R . (1992). Proc. Natl. Acad. Sci. USA, 89, 5408–5412.

  • Okuda T, van Deursen J, Hiebert SW, Grosveld G and Downing JR . (1996). Cell, 84, 321–330.

  • Rotello RJ, Lieberman RC, Purchio AF and Gerschenson LE . (1991). Proc. Natl. Acad. Sci. USA, 88, 3412–3415.

  • Shi M-J and Stavnezer J . (1998). J. Immunol., 161, 6751–6760.

  • Tatematsu M, Yamamoto M, Iwata H, Fukami H, Yuasa H, Tezuka N, Masui T and Nakanishi H . (1993). Jpn. J. Cancer Res., 84, 1258–1264.

  • Yanagihara K and Tsumuraya M . (1992). Cancer Res., 52, 4042–4045.

Download references

Author information

Authors and Affiliations

  1. Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo, Tokyo, 113-0033, Bunkyo-ku, Japan

    Hiroshi Fukamachi

  2. Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore, 117609, Singapore

    Kosei Ito

Authors
  1. Hiroshi Fukamachi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kosei Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroshi Fukamachi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fukamachi, H., Ito, K. Growth regulation of gastric epithelial cells by Runx3. Oncogene 23, 4330–4335 (2004). https://doi.org/10.1038/sj.onc.1207121

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207121

Keywords

This article is cited by

Search

Advanced search

Quick links