Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1999 Dec 1;344(Pt 2):565–570.

Adenomatous polyposis coli protein (APC)-independent regulation of beta-catenin/Tcf-4 mediated transcription in intestinal cells.

J Baulida 1, E Batlle 1, A García De Herreros 1
PMCID: PMC1220676  PMID: 10567241

Abstract

Alterations in the transcriptional activity of the beta-catenin-Tcf complex have been associated with the earlier stages of colonic transformation. We show here that the activation of protein kinase C by the phorbol ester PMA in several intestinal cell lines increases the levels of beta-catenin detected in the nucleus and augments the transcriptional activity mediated by beta-catenin. The response to PMA was not related to modifications in the cytosolic levels of beta-catenin and was observed not only in cells with wild-type adenomatous polyposis coli protein (APC) but also in APC-deficient cells. Binding assays in vitro revealed that PMA facilitates the interaction of the beta-catenin with the nuclear structure. Our results therefore show that beta-catenin-mediated transcription can be regulated independently of the presence of APC.

Full Text

The Full Text of this article is available as a PDF (222.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Batlle E., Verdú J., Domínguez D., del Mont Llosas M., Díaz V., Loukili N., Paciucci R., Alameda F., de Herreros A. G. Protein kinase C-alpha activity inversely modulates invasion and growth of intestinal cells. J Biol Chem. 1998 Jun 12;273(24):15091–15098. doi: 10.1074/jbc.273.24.15091. [DOI] [PubMed] [Google Scholar]
  2. Behrens J., Jerchow B. A., Würtele M., Grimm J., Asbrand C., Wirtz R., Kühl M., Wedlich D., Birchmeier W. Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. Science. 1998 Apr 24;280(5363):596–599. doi: 10.1126/science.280.5363.596. [DOI] [PubMed] [Google Scholar]
  3. Behrens J., von Kries J. P., Kühl M., Bruhn L., Wedlich D., Grosschedl R., Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996 Aug 15;382(6592):638–642. doi: 10.1038/382638a0. [DOI] [PubMed] [Google Scholar]
  4. Brasitus T. A., Bissonnette M. PKC isoforms: villains in colon cancer? Gastroenterology. 1998 Jul;115(1):225–227. doi: 10.1016/s0016-5085(98)70387-7. [DOI] [PubMed] [Google Scholar]
  5. Cadigan K. M., Nusse R. Wnt signaling: a common theme in animal development. Genes Dev. 1997 Dec 15;11(24):3286–3305. doi: 10.1101/gad.11.24.3286. [DOI] [PubMed] [Google Scholar]
  6. Dale T. C. Signal transduction by the Wnt family of ligands. Biochem J. 1998 Jan 15;329(Pt 2):209–223. doi: 10.1042/bj3290209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fabre M., García de Herreros A. Phorbol ester-induced scattering of HT-29 human intestinal cancer cells is associated with down-modulation of E-cadherin. J Cell Sci. 1993 Oct;106(Pt 2):513–521. doi: 10.1242/jcs.106.2.513. [DOI] [PubMed] [Google Scholar]
  8. Fagotto F., Glück U., Gumbiner B. M. Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of beta-catenin. Curr Biol. 1998 Feb 12;8(4):181–190. doi: 10.1016/s0960-9822(98)70082-x. [DOI] [PubMed] [Google Scholar]
  9. Hao X., Tomlinson I., Ilyas M., Palazzo J. P., Talbot I. C. Reciprocity between membranous and nuclear expression of beta-catenin in colorectal tumours. Virchows Arch. 1997 Sep;431(3):167–172. doi: 10.1007/s004280050084. [DOI] [PubMed] [Google Scholar]
  10. He T. C., Sparks A. B., Rago C., Hermeking H., Zawel L., da Costa L. T., Morin P. J., Vogelstein B., Kinzler K. W. Identification of c-MYC as a target of the APC pathway. Science. 1998 Sep 4;281(5382):1509–1512. doi: 10.1126/science.281.5382.1509. [DOI] [PubMed] [Google Scholar]
  11. Ikeda S., Kishida S., Yamamoto H., Murai H., Koyama S., Kikuchi A. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J. 1998 Mar 2;17(5):1371–1384. doi: 10.1093/emboj/17.5.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Korinek V., Barker N., Morin P. J., van Wichen D., de Weger R., Kinzler K. W., Vogelstein B., Clevers H. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science. 1997 Mar 21;275(5307):1784–1787. doi: 10.1126/science.275.5307.1784. [DOI] [PubMed] [Google Scholar]
  13. Lesuffleur T., Barbat A., Dussaulx E., Zweibaum A. Growth adaptation to methotrexate of HT-29 human colon carcinoma cells is associated with their ability to differentiate into columnar absorptive and mucus-secreting cells. Cancer Res. 1990 Oct 1;50(19):6334–6343. [PubMed] [Google Scholar]
  14. Lipkin M. New rodent models for studies of chemopreventive agents. J Cell Biochem Suppl. 1997;28-29:144–147. [PubMed] [Google Scholar]
  15. Mann B., Gelos M., Siedow A., Hanski M. L., Gratchev A., Ilyas M., Bodmer W. F., Moyer M. P., Riecken E. O., Buhr H. J. Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1603–1608. doi: 10.1073/pnas.96.4.1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Morin P. J., Sparks A. B., Korinek V., Barker N., Clevers H., Vogelstein B., Kinzler K. W. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997 Mar 21;275(5307):1787–1790. doi: 10.1126/science.275.5307.1787. [DOI] [PubMed] [Google Scholar]
  17. Morin P. J., Vogelstein B., Kinzler K. W. Apoptosis and APC in colorectal tumorigenesis. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7950–7954. doi: 10.1073/pnas.93.15.7950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Murray N. R., Davidson L. A., Chapkin R. S., Clay Gustafson W., Schattenberg D. G., Fields A. P. Overexpression of protein kinase C betaII induces colonic hyperproliferation and increased sensitivity to colon carcinogenesis. J Cell Biol. 1999 May 17;145(4):699–711. doi: 10.1083/jcb.145.4.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Polakis P. The adenomatous polyposis coli (APC) tumor suppressor. Biochim Biophys Acta. 1997 Jun 7;1332(3):F127–F147. doi: 10.1016/s0304-419x(97)00008-5. [DOI] [PubMed] [Google Scholar]
  20. Sakamoto M., Ino Y., Ochiai A., Kanai Y., Akimoto S., Hirohashi S. Formation of focal adhesion and spreading of polarized human colon cancer cells in association with tyrosine phosphorylation of paxillin in response to phorbol ester. Lab Invest. 1996 Jan;74(1):199–208. [PubMed] [Google Scholar]
  21. Skoudy A., Llosas M. D., García de Herreros A. Intestinal HT-29 cells with dysfunction of E-cadherin show increased pp60src activity and tyrosine phosphorylation of p120-catenin. Biochem J. 1996 Jul 1;317(Pt 1):279–284. doi: 10.1042/bj3170279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Smith K. J., Johnson K. A., Bryan T. M., Hill D. E., Markowitz S., Willson J. K., Paraskeva C., Petersen G. M., Hamilton S. R., Vogelstein B. The APC gene product in normal and tumor cells. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2846–2850. doi: 10.1073/pnas.90.7.2846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tetsu O., McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. 1999 Apr 1;398(6726):422–426. doi: 10.1038/18884. [DOI] [PubMed] [Google Scholar]
  24. Toullec D., Pianetti P., Coste H., Bellevergue P., Grand-Perret T., Ajakane M., Baudet V., Boissin P., Boursier E., Loriolle F. The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C. J Biol Chem. 1991 Aug 25;266(24):15771–15781. [PubMed] [Google Scholar]
  25. Van de Wetering M., Castrop J., Korinek V., Clevers H. Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties. Mol Cell Biol. 1996 Mar;16(3):745–752. doi: 10.1128/mcb.16.3.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Yamamoto H., Kishida S., Uochi T., Ikeda S., Koyama S., Asashima M., Kikuchi A. Axil, a member of the Axin family, interacts with both glycogen synthase kinase 3beta and beta-catenin and inhibits axis formation of Xenopus embryos. Mol Cell Biol. 1998 May;18(5):2867–2875. doi: 10.1128/mcb.18.5.2867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. van de Wetering M., Cavallo R., Dooijes D., van Beest M., van Es J., Loureiro J., Ypma A., Hursh D., Jones T., Bejsovec A. Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell. 1997 Mar 21;88(6):789–799. doi: 10.1016/s0092-8674(00)81925-x. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES