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:

YB-1 facilitates basal and 5-fluorouracil-inducible expression of the human major vault protein (MVP) gene

Oncogene volume 24, pages 3606–3618 (2005)Cite this article

Abstract

Vaults have been suggested to play a direct role in multidrug resistance (MDR) to anticancer drugs. The human major vault protein (MVP) also known as lung resistance-related protein (LRP) represents the predominant component of vaults that may be involved in the defense against xenobiotics. Here, we demonstrate that besides MDR-related cytostatics, also the non-MDR-related drug 5-fluorouracil (5-FU) was able to induce MVP mRNA and protein expression. Treatment with 5-FU amplified the binding activity and interaction of the transcription factor Y-box binding protein-1 (YB-1) with the Y-box of the human MVP gene promoter in a time-dependent manner. 5-FU also induced reporter expressions driven by a panel of newly generated MVP promoter deletion mutants. Interestingly, stably YB-1 overexpressing cell clones showed enhanced binding of YB-1 to the Y-box motif, associated with enhanced basal as well as 5-FU-inducible MVP promoter-driven reporter expressions. Moreover, transduction of YB-1 cDNA led to increased expression of endogenous MVP protein. Under physiological conditions, we observed a strong coexpression of MVP and YB-1 in human colon carcinoma specimen. In summary, our data demonstrate a direct involvement of YB-1 in controlling basal and 5-FU-induced MVP promoter activity. Therefore, YB-1 is directly linked to MVP-mediated drug resistance.

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

  • Asakuno K, Kohno K, Uchiumi T, Kubo T, Sato S, Isono M and Kuwano M . (1994). Biochem. Biophys. Res. Commun., 199, 1428–1435.

  • Bargou RC, Jürchott K, Wagener C, Bergmann S, Metzner S, Bommert K, Mapara MY, Winzer KJ, Dietel M, Dörken B and Royer HD . (1997). Nat. Med., 3, 447–450.

  • Berger W, Elbling L and Micksche M . (2000). Int. J. Cancer, 88, 293–300.

  • Cheng SH, Lam W, Lee ASK, Fung KP, Wu RSS and Fong WF . (2000). Toxicol. Appl. Pharmacol., 64, 134–142.

  • Comerford KM, Wallace TJ, Karhausen J, Louis NA, Montalto MC and Colgan SP . (2002). Cancer Res., 62, 3387–3394.

  • Emre N, Raval-Fernandes S, Kickhoefer VA and Rome LH . (2004). Biochim. Biophys. Acta, 1678, 33–46.

  • Hasegawa SL, Doetsch PW, Hamilton KK, Martin AM, Okenquist SA, Lenz J and Boss JM . (1991). Nucl. Acids Res., 19, 4915–4920.

  • Holm PS, Bergmann S, Jürchott K, Lage H, Brand K, Ladhoff A, Mantwill K, Curiel DT, Dobbelstein M, Dietel M, Gänsbacher B and Royer HD . (2002). J. Biol. Chem., 277, 10427–10434.

  • Hu Y, Stephen AG, Cao J, Tanzer LR, Slapak CA, Harrison SD, Devanarayan V, Dantzig AH, Starling JJ, Rome LH and Moore RE . (2002). Int. J. Cancer, 97, 149–156.

  • Ise T, Nagatani G, Imamura T, Kato K, Takano H, Nomoto M, Izumi H, Ohmori H, Okamoto T, Ohga T, Uchiumi T, Kuwano M and Kohno K . (1999). Cancer Res., 59, 342–346.

  • Izquierdo MA, Scheffer GL, Flens MJ, Giaccone G, Broxterman HJ, Meijer CJ, van der Valk P and Scheper RJ . (1996a). Am. J. Pathol., 148, 877–887.

  • Izquierdo MA, Shoemaker RH, Flens MJ, Scheffer GL, Wu L, Prather TR and Scheper RJ . (1996b). Int. J. Cancer, 65, 230–237.

  • Janz M, Harbeck N, Dettmar P, Berger U, Schmidt A, Jürchott K, Schmitt M and Royer HD . (2002). Int. J. Cancer, 97, 278–282.

  • Jürchott K, Bergmann S, Stein U, Walther W, Janz M, Manni I, Piaggio G, Fietze E, Dietel M and Royer HD . (2003). J. Biol. Chem., 278, 27988–27996.

  • Kickhoefer VA, Rajavel KS, Scheffer GL, Dalton WS, Scheper RJ and Rome LH . (1998). J. Biol. Chem., 273, 8971–8974.

  • Kitazono M, Sumizawa T, Takebayashi Y, Chen ZS, Furukawa T, Nagayama S, Tani A, Takao S, Aikou T and Akiyama S . (1999). J. Natl. Cancer Inst., 91, 1647–1653.

  • Kohno K, Sato S, Takano H, Matsuo K and Kuwano M . (1989). Biochem. Biophys. Res. Commun., 165, 1415–1421.

  • Kohno K, Izumi H, Uchiumi T, Ashizuka M and Kuwano M . (2003). BioEssays, 25, 691–698.

  • Komarov PG, Shtil AA, Holian O, Tee L, Buckingham L, Mechetner EB, Roninson IB and Coon JS . (1998). Oncol. Res., 10, 185–192.

  • Kumar A and Reddy EP . (2001). Gene, 270, 221–229.

  • Kuwano M, Uchiumi T, Hayakawa H, Ono M, Wada M, Izumi H and Kohno K . (2003). Cancer Sci., 94, 9–14.

  • Labialle S, Gayet L, Marthinet E, Rigal D and Baggetto LG . (2002). Biochem. Pharmacol., 64, 943–948.

  • Lange C, Walther W, Schwabe H and Stein U . (2000). Biochem. Biophys. Res. Commun., 278, 125–133.

  • Lasham A, Moloney S, Hale T, Homer C, Zhang YF, Murison JG, Braithwaite AW and Watson J . (2003). J. Biol. Chem., 278, 35516–35523.

  • Laurencot CM, Scheffer GL, Scheper RJ and Shoemaker RH . (1997). Int. J. Cancer, 72, 1021–1026.

  • Meijer GA, Schroeijers AB, Flens MJ, Meuwissen SG, van der Valk P, Baak JP and Scheper RJ . (1999). J. Clin. Pathol., 52, 450–454.

  • Mertens PR, Steinmann K, Alfonso-Jaume MA, En-Nia A, Sun Y and Lovett DH . (2002). J. Biol. Chem., 277, 24875–24882.

  • Meschini S, Marra M, Calcabrini A, Monti E, Gariboldi M, Dolfini E and Arancia G . (2002). Toxicol. In vitro, 16, 389–398.

  • Midgley R and Kerr D . (1999). Lancet, 353, 391–399.

  • Mossink MH, van Zon A, Scheper RJ, Sonneveld P and Wiemer EA . (2003). Oncogene, 22, 7458–7467.

  • Oda Y, Sakamoto A, Shinohara N, Ohga T, Uchiumi T, Kohno K, Tsuneyoshi M, Kuwano M and Iwamoto Y . (1998). Clin. Cancer Res., 4, 2273–2277.

  • Ohga T, Koike K, Ono M, Makino Y, Itagaki Y, Tanimoto M, Kuwano M and Kohno K . (1996). Cancer Res., 56, 4224–4228.

  • Ohga T, Uchiumi T, Makino Y, Koike K, Wada M, Kuwano M and Kohno K . (1998). J. Biol. Chem., 273, 5997–6000.

  • Okamoto T, Izumi H, Imamura T, Takano H, Ise T, Uchiumi T, Kuwano M and Kohno K . (2000). Oncogene, 19, 6194–6202.

  • Pohl G, Filipits M, Suchomel RW, Stranzl T, Depisch D and Pirker R . (1999). Anticancer Res., 19, 5051–5055.

  • Pohl G, Suchomel RW, Stranzl T, Depisch D, Stiglbauer W, Filipits M and Pirker R . (2001). Anticancer Res., 21, 201–204.

  • Scheffer GL, Wijngaard PL, Flens MJ, Izquierdo MA, Slovak ML, Pinedo HM, Meijer CJ, Clevers HC and Scheper RJ . (1995). Nat. Med., 1, 578–582.

  • Scheffer GL, Schroeijers AB, Izquierdo MA, Wiemer EA and Scheper RJ . (2000). Curr. Opin. Oncol., 12, 550–556.

  • Scheper RJ, Broxterman HJ, Scheffer GL, Kaaijk P, Dalton WS, van Heijningen TH, van Kalken CK, Slovak ML, de Vries EG, van der Valk P, Meijer CJLM and Pinedo HM . (1993). Cancer Res., 53, 1475–1479.

  • Schneider J, Gonzalez-Roces S, Pollan M, Lucas R, Tejerina A, Martin M and Alba A . (2001). Breast Cancer Res., 3, 183–191.

  • Schroeijers AB, Scheffer GL, Reurs AW, Pijnenborg AC, Abbondanza C, Wiemer EA and Scheper RL . (2001). J. Histochem. Cytochem., 49, 1379–1385.

  • Scotto KW . (2003). Oncogene, 22, 7496–7511.

  • Shibao K, Takano H, Nakayama Y, Okazaki K, Nagata N, Izumi H, Uchiumi T, Kuwano M, Kohno K and Itoh H . (1999). Int. J. Cancer, 83, 732–737.

  • Stein U, Walther W, Laurencot CM, Scheffer GL, Scheper RJ and Shoemaker RH . (1997). J. Natl. Cancer Inst., 89, 807–813.

  • Stein U, Jürchott K, Walther W, Bergmann S, Schlag PM and Royer HD . (2001). J. Biol. Chem., 276, 28562–28569.

  • Stein U, Jürchott K, Schläfke M and Hohenberger P . (2002). J. Clin. Oncol., 20, 3282–3292.

  • Steiner E, Holzmann K, Pirker C, Elbling L, Micksche M and Berger W . (2004). Biochem. Biophys. Res. Commun., 317, 235–243.

  • Tebbutt NC, Cattell E, Midgley R, Cunningham D and Kerr D . (2002). Eur. J. Cancer, 38, 1000–1015.

  • Wyler B, Shao Y, Schneider E, Cianfriglia M, Scheper RJ, Frey BM, Gieseler F, Schmid T, Twentyman PR and Lehnert M . (1997). Br. J. Haematol., 97, 65–75.

  • Zhang YF, Homer C, Edwards SJ, Hananeia L, Lasham A, Royds J, Sheard P and Braithwaite AW . (2003). Oncogene, 22, 2782–2794.

  • Zijlstra JG, de Vries EG and Mulder NH . (1987). Cancer Res., 47, 1780–1784.

Download references

Acknowledgements

The YB-1 antibody was kindly provided by Karsten Jürchott, Humboldt-University, Berlin. We gratefully acknowledge the excellent technical assistance of Lieselotte Malcherek, Anke Kopacek, and Jutta Aumann.

Author information

Author notes

  1. Stephan Bergmann

    Present address: Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 110, New York, NY, 10021, USA

Authors and Affiliations

  1. Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13092, Berlin, Germany

    Ulrike Stein, Stephan Bergmann & Wolfgang Walther

  2. Department of Pathology, Free University Amsterdam, De Boelelaan 1117, 1007 MB, Amsterdam, The Netherlands

    George L Scheffer & Rik J Scheper

  3. Center of Advanced European Studies and Research (caesar), Ludwig-Erhard-Allee 2, 53175, Bonn, Germany

    Hans-Dieter Royer

  4. Division of Surgery and Surgical Oncology, Charité, Humboldt-University, Campus Berlin-Buch, Robert Rössle Clinic, Lindenberger Weg 80, 13122, Berlin, Germany

    Peter M Schlag

Authors
  1. Ulrike Stein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephan Bergmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George L Scheffer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rik J Scheper
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hans-Dieter Royer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peter M Schlag
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wolfgang Walther
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ulrike Stein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stein, U., Bergmann, S., Scheffer, G. et al. YB-1 facilitates basal and 5-fluorouracil-inducible expression of the human major vault protein (MVP) gene. Oncogene 24, 3606–3618 (2005). https://doi.org/10.1038/sj.onc.1208386

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208386

Keywords

This article is cited by

Search

Advanced search

Quick links