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:

KAI1 promoter activity is dependent on p53, junB and AP2: evidence for a possible mechanism underlying loss of KAI1 expression in cancer cells

Oncogene volume 24, pages 637–649 (2005)Cite this article

Abstract

A molecular mechanism to explain reduced KAI1 expression in invasive and metastatic tumour cells remains elusive. In this report, we extend an earlier study in bladder cells to confirm that a 76 bp region of the KAI1 promoter (residues −922 to −847), with binding motifs for p53, AP1 and AP2, is required for high level activity of a KAI1 reporter in prostate cancer cell lines. Gel shift and supershift experiments supported binding of p53, junB and heterodimers of AP2α/AP2γ or AP2β/AP2γ to this sequence. Introduction of mutations into specific motifs demonstrated an essential requirement for p53 and junB to reporter activity, and that functional synergy between these two factors enhanced activity. A further elevation of reporter activity required AP2. Roles of individual p53, junB and AP2 proteins, as well as functional synergy between p53 and junB, were confirmed in transfection experiments. Western blotting analysis showed that an absence of wild-type p53, and/or a loss of junB and AP2 protein expression, correlated with downregulation of KAI1 mRNA levels in a series of prostate cancer cell lines. A loss of p53 function and/or expression of junB, combined with reduced expression of specific AP2 proteins may underly downregulated KAI1 expression in tumour cells.

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
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Akita H, Iizuka A, Hashimoto Y, Kohri K, Ieda K and Nakanashi M . (2000). Cancer Lett., 153, 79–83.

  • Bergman MR, Cheng S, Honbo N, Piacentini L, Karliner JS and Lovett DH . (2003). Biochem. J., 369, 485–496.

  • Bosher JM, Totty NF, Hsuan JJ, Williams T and Hurst HC . (1996). Oncogene, 13, 1701–1707.

  • Butz K, Shahabeddin L, Geisen C, Spitkovsky D, Ullmann A and Hoppe-Seyler F . (1995). Oncogene, 10, 927–936.

  • Chinenov Y and Kerppola TK . (2001). Oncogene, 20, 2438–2452.

  • Dong JT, Isaacs WB, Barrett JC and Isaacs JT . (1997). Genomics, 41, 25–32.

  • Dong JT, Lamb PW, Rinker-Schaeffer CW, Vukanovic J, Ichikawa T, Isaacs JT and Barrett JC . (1995). Science, 268, 884–886.

  • Dong JT, Suzuki H, Pin SS, Bova S, Schalken J, Isaacs WB, Barrett JC and Isaacs JT . (1996). Cancer Res., 56, 4387–4390.

  • Duriez C, Falette N, Cortes U, Moyret-Lalle C and Puisieux A . (2000). Oncogene, 19, 2461–2464.

  • Gao AC, Lou W, Dong JT, Barrett JC, Danielpour D and Isaacs JT . (2003). Prostate, 57, 256–260.

  • Hilger-Eversheim K, Moser M, Schorle H and Buettner R . (2000). Gene, 260, 1–12.

  • Huang S, Jean D, Luca M, Tainsky MA and Bar-Eli M . (1998). EMBO J., 17, 4358–4369.

  • Jackson P, Grimm MO, Kingsley EA, Brosius U, Antalis T, Yardley G and Russell PJ . (2002). Urol. Oncol., 7, 99–104.

  • Jackson P and Marreiros A . (2004). Progress in Bladder Cancer Research. Columbus F (ed) Nova Science Publishers Inc.: Hauppauge, New York (in press).

    Google Scholar 

  • Jackson P, Millar D, Kingsley E, Yardley G, Ow K, Clark S and Russell PJ . (2000). Cancer Lett., 157, 169–176.

  • Jackson P and Puisieux A . (2000). Biochem. Biophys. Res. Comm., 278, 499–502.

  • Jackson P, Yardley G, Delprado W, Quinn D, Kim K and Russell PJ . (2003). Prost. Cancer Prost. Dis., 6, 174–181.

  • Jean D, Gershenwald JE, Huang S, Luca M, Hudson MJ, Tainsky MA and Bar-Eli M . (1998). J. Biol. Chem., 273, 16501–16508.

  • Li SL, Kim MS, Cherrick HM and Park NH . (1992). Eur. J. Cancer B. Oral. Oncol., 28, 129–134.

  • Lijovic M, Somers G and Frauman AG . (2002). Cancer Detect. Prev., 26, 69–77.

  • Liu FS, Dong JT, Chen JT, Hsieh YT, Ho ESC and Hung MJ . (2000). Gynecol. Oncol., 78, 10–15.

  • Lombardi DP, Geradts J, Foley JF, Chiao C, Lamb PW and Barrett JC . (1999). Cancer Res., 59, 5724–5731.

  • Marreiros A, Czolij R, Yardley G, Crossley M and Jackson P . (2003). Gene, 302, 155–164.

  • Mashimo T, Bandyopadhyay S, Goodarzi G, Watabe S, Pai K, Gross SC and Watabe K . (2000). Biochem. Biophys. Res. Comm., 274, 370–376.

  • Mashimo T, Watabe M, Hirota S, Hosobe S, Miura K, Tegtmeyer P, Rinker-Schaeffer CW and Watabe K . (1998). Proc. Natl. Acad. Sci. USA, 95, 11307–11311.

  • May E, Jenkins JR and May P . (1991). Oncogene, 6, 1363–1365.

  • McPherson LA, Loktev AV and Weigel RJ . (2002). J. Biol. Chem., 277, 45028–45033.

  • McPherson LA and Weigal RJ . (1999). Nucleic Acids Res., 27, 4040–4049.

  • Miyazaki T, Kato H, Shitara Y, Yoshikawa M, Tajima K, Masuda N, Shouji H, Tsukada K, Nakajima T and Kuwano H . (2000). Cancer, 89, 955–962.

  • Ow K, Delprado W, Fisher R, Barrett J, Yu Y, Jackson P and Russell PJ . (2000). J. Pathol., 191, 39–47.

  • Ribeiro JCC, Barnetson AR, Fisher RJ, Mameghan H and Russell PJ . (1997). Int. J. Rad. Biol., 72, 11–20.

  • Ruiz M, Pettaway C, Song R, Stoeltzing O, Ellis L and Bar-Eli M . (2004). Cancer Res., 64, 631–638.

  • Scheffner M, Werness BA, Huibregste JM, Levine AJ and Howley PM . (1990). Cell., 63, 1129–1136.

  • Schindl M, Bachtiary B, Dreier B, Birner P, Latinovic L, Karner B, Breitenecker G and Oberhuber G . (2001). Cancer Lett., 162, 261–266.

  • Sekita N, Suzuki H, Ichikawa T, Kito H, Akakura K, Igarashi T, Nakayama T, Watanabe M, Shiraishi T, Toyota M, Yoshie O and Ito H . (2001). Jap. J. Cancer Res., 92, 947–951.

  • Shaulian E and Karin M . (2002). Nat. Cell. Biol., 4, E131–E135.

  • Shinohara T, Miki T, Nishimura N, Nokihara H, Hamada H, Mukaida N and Sone S . (2001). Cancer Res., 61, 673–678.

  • Tagawa T, Arihiro K, Takeshima Y, Hiyama E, Yamasaki M and Inai K . (1999). Jap. J. Cancer Res., 90, 970–976.

  • Tellez C and Bar-Eli M . (2003). Oncogene, 22, 3130–3137.

  • Van Bokhoven A, Varella-Garcia M, Korch C, Johannes WU, Smith EE, Miller HL, Nordeen SK, Miller GJ and Lucia MS . (2003). Prostate, 57, 205–225.

  • Vandel L, Montreau N, Vial E, Pfarr CM, Binetruy B and Castellazzi M . (1996). Mol. Cell. Biol., 16, 1881–1888.

  • Weijerman PC, Konig JJ, Wong ST, Niesters HG and Peehl DM . (1994). Cancer Res., 54, 5579–5583.

  • White A, Lamb PW and Barrett JC . (1998). Oncogene, 16, 3143–3149.

  • Yardley G, Zauberman A, Oren M and Jackson P . (1998). FEBS Lett., 430, 171–175.

  • Zhao F, Satada M, Licht JD, Hayashixiki Y and Gelb BD . (2001). J. Biol. Chem., 276, 40755–40760.

  • Zhu CH and Domann FE . (2002). Breast Cancer Res. Treat., 71, 47–57.

Download references

Acknowledgements

We thank Dr Kuonosake Watabe (Department of Medical Microbiology and Immunology, Southern Illinois University) for KAI1 promoter reporter plasmids used to initiate these studies, Dr David Lovett (Department of Medicine, San Francisco Veterans Affairs Medical Center) for the junB expression vector, Dr Helen C Hurst (Cancer Research UK, Molecular Oncology Unit, Hammersmith Hospital, UK) for the AP2β expression vector and Dr Ron Weigal (Department of Surgery, Thomas Jefferson University, Philadelphia) for AP2α and AP2γ vectors.

Author information

Authors and Affiliations

  1. Oncology Research Centre, Prince of Wales Hospital, Randwick, NSW, Australia

    Alexandra Marreiros, Kip Dudgeon, Vinh Dao & Paul Jackson

  2. School of Medicine, University of New South Wales, Kensington, NSW, Australia

    Alexandra Marreiros, Kip Dudgeon, Vinh Dao & Paul Jackson

  3. Department of Urology, Heinrich-Heine University, Düsseldorf, Germany

    Marc-Oliver Grimm & Robert Czolij

  4. School of Molecular and Microbial Sciences, University of Sydney, Camperdown, NSW, Australia

    Merlin Crossley

Authors
  1. Alexandra Marreiros
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kip Dudgeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vinh Dao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marc-Oliver Grimm
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert Czolij
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Merlin Crossley
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paul Jackson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul Jackson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marreiros, A., Dudgeon, K., Dao, V. et al. KAI1 promoter activity is dependent on p53, junB and AP2: evidence for a possible mechanism underlying loss of KAI1 expression in cancer cells. Oncogene 24, 637–649 (2005). https://doi.org/10.1038/sj.onc.1208216

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208216

Keywords

This article is cited by

Search

Advanced search

Quick links