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:

Negative regulation of G1/S transition by the candidate bladder tumour suppressor gene DBCCR1

Oncogene volume 20, pages 2956–2964 (2001)Cite this article

Abstract

Deletion of all or part of chromosome 9q is the most common genetic alteration in all stages and grades of bladder cancer. DBCCR1 (deleted in bladder cancer chromosome region candidate 1) maps to the chromosome region 9q32-33, a candidate tumour suppressor locus for bladder cancer. Although no mutations of DBCCR1 have been detected in bladder tumours, expression of DBCCR1 is silenced by promoter hypermethylation in 50% of bladder cancer cell lines analysed. Here we sought to provide functional evidence to authenticate DBCCR1 as a tumour suppressor using gene-transfer methods. Exogenous expression of DBCCR1 protein or an HA epitope-tagged fusion protein, HA-DBCCR1 in NIH3T3 cells and human bladder tumour cell lines resulted in suppression of proliferation. Cell cycle analyses in NIH3T3 cells revealed that DBCCR1-mediated growth inhibition was due to an increase in the number of cells in the G1 phase of the cell cycle. The levels of apoptosis were not altered. These results demonstrate a role for DBCCR1 in cell cycle control, thereby supporting the hypothesis that this is the tumour suppressor gene targeted by 9q32-33 deletion in bladder cancer.

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

Similar content being viewed by others

References

  • Cairns P, Shaw ME, Knowles MA . 1993 Oncogene 8: 1083–1085

  • Dalbagni G, Presti J, Reuter V, Fair WR, Cordon-Cardo C . 1993 Lancet 342: 469–471

  • Di Cristofano A, Pesce B, Cordon-Cardo C, Pandolfi PP . 1998 Nat. Genet. 19: 348–355

  • Ewen ME, Sluss HK, Whitehouse LL, Livingston DM . 1993 Cell 74: 1009–1020

  • Fero ML, Randel E, Gurley KE, Roberts JM, Kemp CJ . 1998 Nature 396: 177–180

  • Habuchi T, Devlin J, Elder PA, Knowles MA . 1995 Oncogene 11: 1671–1674

  • Habuchi T, Luscombe M, Elder PA, Knowles MA . 1998 Genomics 48: 277–288

  • Habuchi T, Takahashi T, Kakinuma H, Wang L, Tsuchiya N, Satoh S, Akao T, Sato K, Ogawa O, Knowles MA, Kato T . 2001 Oncogene in press

  • Habuchi T, Yoshida O, Knowles MA . 1997 Hum. Mol. Genet. 6: 913–919

  • Hartmann A, Moser K, Kriegmair M, Hofstetter A, Hofstaedter F, Knuechel R . 1999 Am. J. Pathol. 154: 721–727

  • Higashitsuji H, Itoh K, Nagao T, Dawson S, Nonoguchi K, Kido T, Mayer RJ, Arii S, Fujita J . 2000 Nat. Med. 6: 96–99

  • Kinzler KW, Vogelstein B . 1996 Cell 87: 159–170

  • Knudson Jr. AG . 1971 Proc. Natl. Acad. Sci. USA 68: 820–823

  • Niman HL, Houghten RA, Walker LE, Reisfeld RA, Wilson IA, Hogle JM, Lerner RA . 1983 Proc. Natl. Acad. Sci. USA 80: 4949–4953

  • Nishiyama H, Hornigold N, Davies AM, Knowles MA . 1999a Genomics 59: 335–338

  • Nishiyama H, Itoh K, Kaneko Y, Kishishita M, Yoshida O, Fujita J . 1997 J. Cell Biol. 137: 899–908

  • Nishiyama H, Takahashi T, Kakehi Y, Habuchi T, Knowles MA . 1999b Genes Chromo. Cancer 26: 171–175

  • Office for National Statistics . 1996 ONS monitor MB1 96/1

  • Olumi AF, Tsai YC, Nichols PW, Skinner DG, Cain DR, Bender LI, Jones PA . 1990 Cancer Res. 50: 7081–7083

  • Parker S, Tong T, Balder S, Wingo P . 1997 CA Cancer J. Clin. 47: 5–27

  • Pestov DG, Polonskaia M, Lau LF . 1999 Biotechniques 26: 102–106

  • Ravitz MJ, Wenner CE . 1997 Adv. Cancer Res. 71: 165–207

  • Roussel MF . 1999 Oncogene 18: 5311–5317

  • Salem C, Liang G, Tsai YC, Coulter J, Knowles MA, Feng AC, Groshen S, Nichols PW, Jones PA . 2000 Cancer Res. 60: 2473–2476

  • Simoneau M, Aboulkassim TO, LaRue H, Rousseau F, Fradet Y . 1999 Oncogene 18: 157–163

  • Sionov RV, Haupt Y . 1999 Oncogene 18: 6145–6157

  • Williamson MP, Elder PA, Shaw ME, Devlin J, Knowles MA . 1995 Hum. Mol. Gene. 4: 1569–1577

  • Wu SQ, Storer BE, Bookland EA, Klingelhutz AJ, Gilchrist KW, Meisner LF, Oyasu R, Reznikoff CA . 1991 Cancer Res. 51: 3323–3326

Download references

Acknowledgements

We are grateful to Dr D Pestov, Dr K Maruyama, and Dr J Fujita for providing expression constructs. We also thank Dr K Sibley and Dr NJ Hornigold for helpful suggestions in the preparation of the manuscript. This work was supported by the Imperial Cancer Research Fund.

Author information

Authors and Affiliations

  1. ICRF Clinical Centre, St. James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK

    Hiroyuki Nishiyama, Jason H Gill, Eva Pitt, Wendy Kennedy & Margaret A Knowles

Authors
  1. Hiroyuki Nishiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jason H Gill
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eva Pitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wendy Kennedy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Margaret A Knowles
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nishiyama, H., Gill, J., Pitt, E. et al. Negative regulation of G1/S transition by the candidate bladder tumour suppressor gene DBCCR1. Oncogene 20, 2956–2964 (2001). https://doi.org/10.1038/sj.onc.1204432

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204432

Keywords

This article is cited by

Search

Advanced search

Quick links