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.

  • Short Report
  • Published:

Expression of the gut-enriched Krüppel-like factor (Krüppel-like factor 4) gene in the human colon cancer cell line RKO is dependent on CDX2

Oncogene volume 20, pages 4884–4890 (2001)Cite this article

Abstract

Gut-enriched Krüppel-like factor (GKLF or KLF4) is a zinc finger-containing, epithelial-specific transcription factor, that functions as a suppressor of cell proliferation. We previously showed that GKLF expression is decreased in intestinal and colonic adenomas, respectively, from multiple intestinal neoplasia (Min) mice and familial adenomatous polyposis (FAP) patients. This study shows that GKLF is induced upon activation of the adenomatous polyposis coli (APC) gene. However, among several human colon cancer cell lines surveyed, expression of GKLF is lowest in RKO, a line with wild-type APC and β-catenin. RKO contains a mutated allele that encodes the putative tumor suppressor homeodomain protein, CDX2. We show that wild-type CDX2 activates the GKLF promoter and that the mutated CDX2 has a dominant negative effect on wild-type function. Our results may help explain the exceedingly low levels of GKLF expression detected in this cell line, which may in turn contribute to the tumor phenotype.

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

  • Adam PJ, Regan CP, Hautmann MB, Owens GK . 2000 J. Biol. Chem. 275: 37798–37806

  • Beck F, Chawengsaksophak K, Waring P, Playford RJ, Furness JB . 1999 Proc. Natl. Acad. Sci. USA 96: 7318–7323

  • Chawengsaksophak K, James R, Hammond VE, Kontgen F, Beck F . 1997 Nature 386: 84–87

  • Conkright MD, Wani MA, Anderson KP, Lingrel JB . 1999 Nucl. Acids Res. 27: 1263–1270

  • Da Costa LT, He TC, Yu J, Sparks AB, Morin PJ, Polyak K, Laken S, Vogelstein B, Kinzler KW . 1999 Oncogene 18: 5010–5014

  • Dang DT, Pevsner J, Yang VW . 2000a Intl. J. Biochem. Cell Biol. 32: 1103–1121

  • Dang DT, Bachman KE, Mahatan CS, Dang LH, Giardiello FM, Yang VW . 2000b FEBS Lett. 476: 203–207

  • Duluc I, Lorentz O, Fritsch C, Leberquier C, Kedinger M, Freund JN . 1997 J. Cell. Sci. 110: 1317–1324

  • Duprey P, Chowdhury K, Dressler GR, Balling R, Simon D, Guenet JL, Gruss P . 1988 Genes Dev. 2: 1647–1654

  • Ee HC, Erler T, Bathal PS, Young GP, James RJ . 1995 Am. J. Pathol. 147: 586–592

  • Fang R, Santiago NA, Olds LC, Sibley E . 2000 Gastroenterology 118: 115–127

  • Garrett-Sinha LA, Eberspaecher H, Seldin MF, de Crombrugghe B . 1996 J. Biol. Chem. 271: 31384–31390

  • Gehring WJ, Qian YQ, Billeter M, Furukubo-Tokunaga K, Schier AF, Resendez-Perez D, Affolter M, Otting G, Wüthrich K . 1994 Cell 78: 211–223

  • Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H, Joslyn G, Stevens J, Spirio L, Robertson M . 1991 Cell 66: 589–600

  • He TC, Sparks AB, Rago C, Hermeking H, Zawel L, Da Costa LT, Morin PJ, Vogelstein B, Kinzler KW . 1998 Science 281: 1509–1512

  • He TC, Chan TA, Vogelstein B, Kinzler KW . 1999 Cell 99: 335–345

  • Ichii S, Horii A, Nakatsuru S, Furuyama J, Utsunomiya J, Nakamura Y . 1992 Human Mol. Genet. 1: 387–390

  • James R, Erler T, Kazenwadel J . 1994 J. Biol. Chem. 269: 15229–15237

  • Jenkins TD, Opitz OG, Okano J, Rustgi AK . 1998 J. Biol. Chem. 273: 10747–10754

  • Joslyn G, Carlson M, Thliveris A, Albertsen H, Gelberg L, Samowitz W, Groden J, Stevens J, Spirio L, Robertson M . 1991 Cell 66: 601–613

  • Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hedge P, McKechnie D, Finniear R, Markham A, Froffen J, Boguski MS, Altschul SF, Horaii A, Ando H, Kyoshi Y, Miki Y, Nishisho I, Nakamura Y . 1991 Science 253: 661–665

  • Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B, Clevers H . 1997 Science 275: 1784–1787

  • Lickert H, Domon C, Huls G, Wehrle C, Duluc I, Clevers H, Meyer BI, Freund JN, Kemler R . 2000 Development 127: 3805–3813

  • Lorentz O, Duluc I, Arcangelis AD, Simon-Assmann P, Kedinger M, Preund JN . 1997 J. Cell Biol. 139: 1553–1565

  • Mahatan CS, Kaestner KH, Geiman DE, Yang VW . 1999 Nucl. Acids Res. 27: 4562–4569

  • Mallo GV, Rechreche H, Frigerio JM, Rocha D, Zweibaum A, Lacasa M, Jordan BR, Dusetti NJ, Dagorn JC, Iovanna JL . 1997 Int. J. Cancer 74: 35–44

  • Mallo GV, Soubeyran P, Lissitzky JC, Andre F, Farmarier C, Marvaldi J, Dagarn JC, Iovanna JL . 1998 J. Biol. Chem. 273: 14030–14036

  • Morin PJ, Vogelstein B, Kinzler KW . 1996 Proc. Natl. Acad. Sci. USA 93: 7950–7954

  • Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW . 1997 Science 275: 1787–1790

  • Moser AR, Pitot HC, Dove WF . 1990 Science 247: 322–324

  • Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P, Markham A, Krush AJ, Perterson G, Hamilton SR, Nilber DB, Levy MC, Bryan TM, Preisinger AC, Smith KJ, Su LK, Kinzler KW, Vogelstein B . 1991 Science 253: 665–669

  • Polakis P . 2000 Genes Dev. 14: 1837–1851

  • Segre JA, Bauer C, Fuchs E . 1999 Nature Genet. 22: 356–360

  • Shie JL, Chen ZY, Fu M, Pestell RG, Tseng CC . 2000a Nucl. Acids Res. 28: 2969–2976

  • Shie JL, Chen ZY, O'Brien MJ, Pestell RG, Lee ME, Tseng CC . 2000b Am. J. Physiol. Gastrointest. Liver Physiol. 279: G806–G814

  • Shields JM, Christy RJ, Yang VW . 1996 J. Biol. Chem. 271: 20009–20017

  • Silberg DG, Swain GP, Suh ER, Traber PG . 2000 Gastroenterology 119: 961–971

  • Suh ER, Traber PG . 1996 Mol. Cell. Biol. 16: 619–625

  • Suh ER, Chen L, Taylor J, Traber PG . 1994 Molec. Cell. Biol. 14: 7340–7351

  • Sun R, Chen X, Yang VW . 2001 J. Biol. Chem. 276: 6897–6900

  • Tamai Y, Nakajima R, Ishikawa T, Takaku K, Seldin MF, Taketo MM . 1999 Cancer Res. 59: 2965–2970

  • Tetsu O, McCormick F . 1999 Nature 398: 422–426

  • Ton-That H, Kaestner KH, Shields JM, Mahatanankoon CS, Yang VW . 1997 FEBS Lett. 419: 239–243

  • Wicking C, Simms LA, Evans T, Walsh M, Chawengsaksophak K, Beck F, Chenevix-Trench G, Young J, Jass J, Leggett B, Wainwright B . 1998 Oncogene 17: 657–659

  • Zhang W, Geiman DE, Shields JM, Dang DT, Mahatan CS, Kaestner KH, Biggs JR, Kraft AS, Yang VW . 2000 J. Biol. Chem. 275: 18391–18398

Download references

Acknowledgements

We are indebted to Dr Bert Vogelstein for generously providing HT29–APC and HT29–β-Gal cell lines; the SI–PGL3–luciferase; TCF3 WT and mutant-pGL3–luciferase reporters; and the mutant β-catenin (S33Y), wild-type and mutant CDX2 expression vectors; Drs Kurtis Bachman and Paul Corn for providing colorectal cancer cell lines; Dr Kallayanee Chawengsaksophak for the CDX2 genomic clone; and Dr Anil Rustgi for the human GKLF cDNA plasmid. This work was partially funded by NIH Grants CA84197, DK52230 and DK10020. DT Dang is a recipient of the Stanley J. Sarnoff Endowment for the Cardiovascular Sciences Scholar Award. IA Agboola was supported by the Minority Summer Internship Program of the Johns Hopkins University.

Author information

Authors and Affiliations

  1. Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, MD, USA

    Duyen T Dang, Channing S Mahatan, Iyabode A Agboola & Vincent W Yang

  2. The Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, MD, USA

    Long H Dang & Vincent W Yang

  3. Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, MD, USA

    Vincent W Yang

Authors
  1. Duyen T Dang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Channing S Mahatan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Long H Dang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Iyabode A Agboola
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vincent W Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vincent W Yang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dang, D., Mahatan, C., Dang, L. et al. Expression of the gut-enriched Krüppel-like factor (Krüppel-like factor 4) gene in the human colon cancer cell line RKO is dependent on CDX2. Oncogene 20, 4884–4890 (2001). https://doi.org/10.1038/sj.onc.1204645

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204645

Keywords

This article is cited by

Search

Advanced search

Quick links