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.

  • Original Paper
  • Published:

Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity

Abstract

Krüppel-like factor 4 (KLF4) is a zinc-finger-containing transcription factor, the expression of which is enriched in the postmitotic cells of the intestinal epithelium. KLF4 is a target gene of the tumor suppressor adenomatous polyposis coli (APC). We sought to determine the role of KLF4 in suppressing the tumorigenecity of RKO colon cancer cells, which do not express KLF4. We utilized an established system in RKO cells, in which an inducible promoter controls expression of KLF4. Four independent assays were used to assess the effects of KLF4 induction on tumor cells. We find that KLF4 overexpression reduces colony formation, cell migration and invasion, and in vivo tumorigenecity. The mechanism of action of KLF4 does not involve apoptosis. These findings, along with our previous findings that KLF4 induces G1/S arrest, suggest that KLF4 is a cell cycle checkpoint protein that can reduce tumorigenecity of colon cancer cells.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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 and Owens GK . (2000). J. Biol. Chem., 275, 37798–37806.

  • Behr R and Kaestner KH . (2002). Mech. Dev., 115, 167–169.

  • Brembeck FH and Rustgi AK . (2000). J. Biol. Chem., 275, 28230–28239.

  • Chen X, Johns DC, Geiman DE, Marban E, Dang DT, Hamlin G, Sun R and Yang VW . (2001). J. Biol. Chem., 276, 30423–30428.

  • Chen ZY, Shie J and Tseng C . (2000). FEBS Lett., 477, 67–72.

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

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

  • Dang DT, Mahatan CS, Dang LH, Agboola IA and Yang VW . (2001). Oncogene, 20, 4884–4890.

  • Dang DT, Zhao W, Mahatan CS, Geiman DE and Yang VW . (2002). Nucleic Acids Res., 30, 2736–2741.

  • Foster KW, Frost AR, McKie-Bell P, Lin CY, Engler JA, Grizzle WE and Ruppert JM . (2000). Cancer Res., 60, 6488–6495.

  • Foster KW, Ren S, Louro ID, Lobo-Ruppert SM, McKie-Bell P, Grizzle W, Hayes MR, Broker TR, Chow LT and, Ruppert JM . (1999). Cell Growth Differ., 10, 423–434.

  • Geiman DE, Ton-That H, Johnson JM and Yang VW . (2000). Nucleic Acids Res., 28, 1106–1113.

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

  • Katz JP, Perreault N, Goldstein BG, Lee CS, Labosky PA, Yang VW and Kaestner KH . (2002). Development, 129, 2619–2628.

  • Liu B, Nicolaides NC, Markowitz S, Willson JK, Parsons RE, Jen J, Papadopolous N, Peltomaki P, de la Chapelle A, Hamilton SR, Kinzler KW and Vogelstein B . (1995). Nat. Genet., 9, 48–55.

  • Luo J, Dunn T, Ewing C, Sauvageot J, Chen Y, Trent J and Isaacs W . (2002). Prostate, 51, 189–200.

  • Nickenig G, Baudler S, Muller C, Werner C, Werner N, Welzel H, Strehlow K and Bohm M . (2002). FASEB J., 16, 1077–1086.

  • No D, Yao TP and Evans RM . (1996). Proc. Natl. Acad. Sci. USA, 93, 3346–3351.

  • Panigada M, Porcellini S, Sutti F, Doneda L, Pozzoli O, Consalez GG, Guttinger M and Grassi F . (1999). Mech. Dev., 81, 103–113.

  • Pouliot N, Nice EC and Burgess AW . (2001). Exp. Cell Res., 266, 1–10.

  • Rigas A, Dervenis C, Giannakou N, Kozoni V, Shiff SJ and Rigas B . (2002). Cancer Invest., 20, 657–665.

  • Rozic JG, Chakraborty C and Lala PK . (2001). Int. J. Cancer, 93, 497–506.

  • Segre JA, Bauer C and Fuchs E . (1999). Nat. Genet., 22, 356–360.

  • Shie JL, Chen ZY, Fu M, Pestell RG and Tseng CC . (2000a). Nucleic Acids Res., 28, 2969–2976.

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

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

  • Suh E and Traber PG . (1996). Mol. Cell. Biol., 16, 619–625.

  • Veigl ML, Kasturi L, Olechnowicz J, Ma AH, Lutterbaugh JD, Periyasamy S, Li GM, Drummond J, Modrich PL, Sedwick WD and Markowitz SD . (1998). Proc. Natl. Acad. Sci. USA, 95, 8698–8702.

  • Yet SF, McA'Nulty MM, Folta SC, Yen HW, Yoshizumi M, Hsieh CM, Layne MD, Chin MT, Wang H, Perrella MA, Jain MK and Lee ME . (1998). J. Biol. Chem., 273, 1026–1031.

  • Yoon HS, Chen X and Yang VW . (2003). J. Biol. Chem., 278, 2101–2105.

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

Download references

Acknowledgements

We thank Leslie Metzger (Johns Hopkins Oncology Center Cell Imaging Core Facility), Boris Baibakov, and Olga Kovbasnjuk (Johns Hopkins Gastroenterology Confocal Facility) for assistance with FACS analysis and microscopy. This work is supported by the National Institutes of Health Grants DK59970 (DTD), DK52230, and CA84197 (VWY). DTD is a recipient of the Research Scholar Award from the American Gastroenterology Association and the Basic Research Award from the Glaxo Institute for Digestive Health. VWY is a recipient of the Georgia Cancer Coalition Distinguished Cancer Clinician Scientist Award.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Duyen T Dang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dang, D., Chen, X., Feng, J. et al. Overexpression of Krüppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity. Oncogene 22, 3424–3430 (2003). https://doi.org/10.1038/sj.onc.1206413

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206413

Keywords

This article is cited by

Search

Quick links