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:

Tumor suppressor activity of RUNX3

Abstract

Recent analyses have revealed that RUNX family members play important roles in both normal developmental processes and carcinogenesis. Of the three known RUNX family members, RUNX3 has been shown to be involved in neurogenesis of the dorsal root ganglia, T-cell differentiation and tumorigenesis of gastric epithelium. Deletion of the Runx3 locus in mice resulted in hyperplasia of the gastric epithelium due to the stimulation of proliferation and suppression of apoptosis that was accompanied by a reduced sensitivity to TGF-β1. In primary human gastric cancer specimens, RUNX3 is frequently inactivated by allele loss or gene silencing due to promoter hypermethylation. The tumorigenicity of human gastric cancer cell lines in nude mice decreased as the level of RUNX3 expression increased, which indicates that RUNX3 is a bona fide tumor suppressor of gastric cancers.

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

Access options

Buy this article

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

Similar content being viewed by others

References

  • Alexandrow MG and Moses HL . (1995). Cancer Res., 55, 1452–1457.

  • Atfi A, Buisine M, Mazars A and Gespach C . (1997). J. Biol. Chem., 272, 24731–24734.

  • Bae SC and Lee J . (2000). Gene, 241, 255–258.

  • Bae SC, Takahashi E, Zhang YW, Ogawa E, Shigesada K, Namba Y, Satake M and Ito Y . (1995). Gene, 159, 245–248.

  • Bangsow C, Rubins N, Glusman G, Bernstein Y, Negreanu V, Goldenberg D, Lotem J, Ben Asher E, Lancet D, Levanon D and Groner Y . (2001). Gene, 279, 221–232.

  • Brown R and Strathdee G . (2002). Trends Mol. Med., 8, S43–S48.

  • Cameron EE, Bachman KE, Myohanen S, Herman JG and Baylin SB . (1999). Nat. Genet., 21, 103–107.

  • Cameron ER, Blyth K, Hanlon L, Kilbey A, Mackay N, Stewart M, Terry A, Vaillant F, Wotton S and Neil JC . (2003). Blood Cells Mol. Dis., 30, 194–200.

  • Chalaux E, Lopez-Rovira T, Rosa JL, Pons G, Boxer LM, Bartrons R and Ventura F . (1999). FEBS Lett., 457, 478–482.

  • Chen CR, Kang Y and Massague J . (2001). Proc. Natl. Acad. Sci. USA, 98, 992–999.

  • Chipuk JE, Bhat M, Hsing AY, Ma J and Danielpour D . (2001). J. Biol. Chem., 276, 26614–26621.

  • Claassen GF and Hann SR . (2000). Proc. Natl. Acad. Sci. USA, 97, 9498–9503.

  • Cohen Jr MM . (2003). Am. J. Med. Genet., 116A, 1–10.

  • Ducy P, Zhang R, Geoffroy V, Ridall AL and Karsenty G . (1997). Cell, 89, 747–754.

  • 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.

  • Gayther SA, Batley SJ, Linger L, Bannister A, Thorpe K, Chin SF, Daigo Y, Russell P, Wilson A, Sowter HM, Delhanty JD, Ponder BA, Kouzarides T and Caldas C . (2000). Nat. Genet., 24, 300–303.

  • Guo WH, Weng LQ, Ito K, Chen LF, Nakanishi H, Tatematsu M and Ito Y . (2002). Oncogene, 21, 8351–8355.

  • Hammerschmidt W and Sugden B . (1989). Nature, 340, 393–397.

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

  • Herzog CR, Wang Y and You M . (1995). Oncogene, 11, 1811–1815.

  • Hess J, Porte D, Munz C and Angel P . (2001). J. Biol. Chem., 276, 20029–20038.

  • Imai S, Koizumi S, Sugiura M, Tokunaga M, Uemura Y, Yamamoto N, Tanaka S, Sato E and Osato T . (1994). Proc. Natl. Acad. Sci. USA, 91, 9131–9135.

  • Inoue K, Ozaki S, Shiga T, Ito K, Masuda T, Okado N, Iseda T, Kawaguchi S, Ogawa M, Bae SC, Yamashita N, Itohara S, Kudo N and Ito Y . (2002). Nat. Neurosci., 5, 946–954.

  • Ito Y and Miyazono K . (2003). Curr. Opin. Genet. Dev., 13, 43–47.

  • Johannsen E, Koh E, Mosialos G, Tong X, Kieff E and Grossman SR . (1995). J. Virol., 69, 253–262.

  • Jones PA and Laird PW . (1999). Nat. Genet., 21, 163–167.

  • Kaiser C, Laux G, Eick D, Jochner N, Bornkamm GW and Kempkes B . (1999). J. Virol., 73, 4481–4484.

  • Kato N, Tamura G, Fukase M, Shibuya H and Motoyama T . (2003). Am. J. Pathol., 163, 387–391.

  • Kim R, Trubetskoy A, Suzuki T, Jenkins NA, Copeland NG and Lenz J . (2003). J. Virol., 77, 2056–2062.

  • Kitabayashi I, Yokoyama A, Shimizu K and Ohki M . (1998). EMBO J., 17, 2994–3004.

  • 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.

  • Kuniyasu H, Yasui W, Yokozaki H, Akagi M, Akama Y, Kitahara K, Fujii K and Tahara E . (1994). Int. J. Cancer, 59, 597–600.

  • Lee KS, Kim HJ, Li QL, Chi XZ, Ueta C, Komori T, Wozney JM, Kim EG, Choi JY, Ryoo HM and Bae SC . (2000). Mol. Cell. Biol., 20, 8783–8792.

  • 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, Negreanu V, Bernstein Y, Bar-Am I, Avivi L and Groner Y . (1994). Genomics, 23, 425–432.

  • Li QL, Ito K, Sakakura C, Fukamachi H, Inoue K, Chi XZ, Lee KY, Nomura S, Lee CW, Han SB, Kim HM, Kim WJ, 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 SC and Ito Y . (2002). Cell, 109, 113–124.

  • Liberati NT, Datto MB, Frederick JP, Shen X, Wong C, Rougier-Chapman EM and Wang XF . (1999). Proc. Natl. Acad. Sci. USA, 96, 4844–4849.

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

  • Lund AH and van Lohuizen M . (2002). Cancer Cell, 1, 213–215.

  • 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.

  • Nam S, Jin YH, Li QL, Lee KY, Jeong GB, Ito Y, Lee J and Bae SC . (2002). Mol. Cell. Biol., 22, 547–554.

  • North T, Gu TL, Stacy T, Wang Q, Howard L, Binder M, Marin-Padilla M and Speck NA . (1999). Development, 126, 2563–2575.

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

  • Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB and Owen MJ . (1997). Cell, 89, 765–771.

  • Parkin DM, Pisani P and Ferlay J . (1999). Int. J. Cancer, 80, 827–841.

  • Robertson AJ, Dickey CE, McCarthy JJ and Coffman JA . (2002). Mech. Dev., 117, 327–330.

  • Sano T, Tsujino T, Yoshida K, Nakayama H, Haruma K, Ito H, Nakamura Y, Kajiyama G and Tahara E . (1991). Cancer Res., 51, 2926–2931.

  • Schuster N and Krieglstein K . (2002). Cell Tissue Res., 307, 1–14.

  • Sherr CJ . (1996). Science, 274, 1672–1677.

  • Spender LC, Cornish GH, Sullivan A and Farrell PJ . (2002). J. Virol., 76, 4919–4927.

  • Spieker N, Beitsma M, Van Sluis P, Chan A, Caron H and Versteeg R . (2001). Genes Chromosomes Cancer, 31, 172–181.

  • Stewart M, Mackay N, Cameron ER and Neil JC . (2002). J. Virol., 76, 4364–4369.

  • Stewart M, Terry A, Hu M, O’Hara M, Blyth K, Baxter E, Cameron E, Onions DE and Neil JC . (1997). Proc. Natl. Acad. Sci. USA, 94, 8646–8651.

  • Tanaka K, Yanoshita R, Konishi M, Oshimura M, Maeda Y, Mori T and Miyaki M . (1993). Oncogene, 8, 2253–2258.

  • Taniuchi I, Osato M, Egawa T, Sunshine MJ, Bae SC, Komori T, Ito Y and Littman DR . (2002). Cell, 111, 621–633.

  • Teitz T, Wei T, Valentine MB, Vanin EF, Grenet J, Valentine VA, Behm FG, Look AT, Lahti JM and Kidd VJ . (2000). Nat. Med., 6, 529–535.

  • Teramoto T, Kiss A and Thorgeirsson SS . (1998). Biochem. Biophys. Res. Commun., 251, 56–60.

  • Uchino S, Tsuda H, Noguchi M, Yokota J, Terada M, Saito T, Kobayashi M, Sugimura T and Hirohashi S . (1992). Cancer Res., 52, 3099–3102.

  • Waki T, Tamura G, Sato M, Terashima M, Nishizuka S and Motoyama T . (2003). Cancer Sci., 94, 360–364.

  • Wang Q, Stacy T, Binder M, Marin-Padilla M, Sharpe AH and Speck NA . (1996). Proc. Natl. Acad. Sci. USA, 93, 3444–3449.

  • Warner BJ, Blain SW, Seoane J and Massague J . (1999). Mol. Cell. Biol., 19, 5913–5922.

  • Weinberg RA . (1995). Cell, 81, 323–330.

  • Weith A, Brodeur GM, Bruns GA, Matise TC, Mischke D, Nizetic D, Seldin MF, van Roy N and Vance J . (1996). Cytogenet. Cell Genet., 72, 114–144.

  • Woolf E, Xiao C, Fainaru O, Lotem J, Rosen D, Negreanu V, Bernstein Y, Goldenberg D, Brenner O, Berke G, Levanon D and Groner Y . (2003). Proc. Natl. Acad. Sci. USA, 100, 7731–7736.

  • Wotton S, Stewart M, Blyth K, Vaillant F, Kilbey A, Neil JC and Cameron ER . (2002). Cancer Res., 62, 7181–7185.

  • Yamamura Y, Hua X, Bergelson S and Lodish HF . (2000). J. Biol. Chem., 275, 36295–36302.

  • Yokomizo T, Ogawa M, Osato M, Kanno T, Yoshida H, Fujimoto T, Fraser S, Nishikawa S, Okada H, Satake M, Noda T, Nishikawa S and Ito Y . (2001). Genes Cells, 6, 13–23.

  • Zhang Y, Feng XH and Derynck R . (1998). Nature, 394, 909–913.

  • Zhang YW, Yasui N, Ito K, Huang G, Fujii M, Hanai J, Nogami H, Ochi T, Miyazono K and Ito Y . (2000). Proc. Natl. Acad. Sci. USA, 97, 10549–10554.

Download references

Acknowledgements

This work was supported by financial aid from the Creative Research Program (M10301000012) of the Ministry of Science and Technology of Korea to S-C Bae

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Suk-Chul Bae.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bae, SC., Choi, JK. Tumor suppressor activity of RUNX3. Oncogene 23, 4336–4340 (2004). https://doi.org/10.1038/sj.onc.1207286

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207286

Keywords

This article is cited by

Search

Quick links