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:

Cyclin B1 depletion inhibits proliferation and induces apoptosis in human tumor cells

Abstract

Cyclin B1 is the regulatory subunit of M-phase promoting factor, and proper regulation of cyclin B1 is essential for the initiation of mitosis. Increasing evidence indicates that the deregulation of cyclin B1 is involved in neoplastic transformation, suggesting the suppression of cyclin B1 could be an attractive strategy for antiproliferative therapy. In the present work, we analysed the impact of small interfering RNAs (siRNAs) targeted to cyclin B1 on different human tumor cell lines. Cyclin B1 siRNAs reduced the protein level of cyclin B1 in HeLa, MCF-7, BT-474 and MDA-MB-435 tumor cells and efficiently reduced the kinase activity of Cdc2/cyclin B1 in HeLa cells. siRNA-treated cells were arrested in G2/M phase in all tumor cell lines tested. Proliferation of tumor cells from different origins was suppressed by 50–80% 48 h after transfection and apoptosis was increased from 5 to 40–50%. Furthermore, tumor cells showed less colony-forming ability after siRNA treatment. In contrast, primary human umbilical vein endothelial cells exhibited only a slight change in cell cycle, and neither apoptosis nor clear inhibition of proliferation was observed after cyclin B1 siRNA treatment for 48 h. These results indicate that siRNAs against cyclin B1 could become a powerful antiproliferative tool in future antitumor therapy.

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
Figure 5
Figure 6

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  • Cogswell JP, Brown CE, Bisi JE and Neill SD . (2000). Cell Growth Differ., 11, 615–623.

  • Davies TG, Bentley J, Arris CE, Boyle FT, Curtin NJ, Endicott JA, Gibson AE, Golding BT, Griffin RJ, Hardcastle IR, Jewsbury P, Johnson LN, Mesguiche V, Newell DR, Noble ME, Tucker JA, Wang L and Whitfield HJ . (2002). Nat. Struct. Biol., 9, 745–749.

  • Dong Y, Sui L, Watanabe Y, Sugimoto K and Tokuda M . (2002). Cancer Lett., 177, 13–19.

  • Hassan KA, Ang KK, El-Naggar AK, Story MD, Lee JI, Liu D, Hong WK and Mao L . (2002). Cancer Res., 62, 6414–6417.

  • Jin P, Hardy S and Morgan DO . (1998). J. Cell Biol., 141, 875–885.

  • Knockaert M, Lenormand P, Gray N, Schultz P, Pouyssegur J and Meijer L . (2002). Oncogene, 21, 6413–6424.

  • Krek W and Nigg EA . (1991). EMBO J., 10, 3331–3341.

  • Lane H and Nigg EA . (1996). J. Cell Biol., 135, 1701–1713.

  • Li JQ, Kubo A, Wu F, Usuki H, Fujita J, Bandoh S, Masaki T, Saoo K, Takeuchi H, Kobayashi S, Imaida K, Maeta H, Ishida T and Kuriyama S . (2003). Int. J. Oncol., 22, 1101–1110.

  • Liu X and Erikson RL . (2003). Proc. Natl. Acad. Sci. USA, 100, 5789–5794.

  • McManus MT and Sharp PA . (2002). Nat. Rev. Genet., 3, 737–747.

  • Park M, Chae HD, Yun J, Jung M, Kim S, Kim SH, Han MH and Shin DY . (2000). Cancer Res., 60, 542–545.

  • Santana C, Ortega E and Garcia-Carranca A . (2002). Mutat. Res., 508, 49–58.

  • Sarafan-Vasseur N, Lamy A, Bourguignon J, Le Pessor F, Hieter P, Sesboüe R, Bastard C, Frebourg T and Flaman JM . (2002). Oncogene, 21, 2051–2057.

  • Spankuch-Schmitt B, Bereiter-Hahn J, Kaufmann M and Strebhardt K . (2002). J. Natl. Cancer Inst., 94, 1863–1877.

  • Takeno S, Noguchi T, Kikuchi R, Uchida Y, Yokoyama S and Muller W . (2002). Cancer, 94, 2874–2881.

  • Tuschl T . (2002). Nat. Biotechnol., 20, 446–448.

  • Yin XY, Grove L, Datta NS, Katula K, Long MW and Prochownik EV . (2001). Cancer Res., 61, 6487–6493.

  • Yuan J, Eckerdt F, Bereiter-Hahn J, Kurunci-Csacsko E, Kaufmann M and Strebhardt K . (2002b). Oncogene, 21, 8282–8292.

  • Yuan J, Krämer A, Eckerdt F, Kaufmann M and Strebhardt K . (2002a). Cancer Res., 62, 4186–4190.

Download references

Acknowledgements

We thank Katharina Kourtis for her excellent technical support with apoptosis analysis. We are also grateful to Dr Bernd Martin for his critical reading and to Dr Barbara J Rutledge for editing assistance. This work is supported in part by the Nationales Genomforschungsnetz (Grant KR-S07T01 to KS), the Deutsche Krebshilfe (Grant 10-1212-St 1 to KS), the Deutsche Forschungsgemeinschaft (grant STR/8-1 to KS), the Messer Stiftung, the Sander Stiftung and the Dresdner Bank.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Klaus Strebhardt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yuan, J., Yan, R., Krämer, A. et al. Cyclin B1 depletion inhibits proliferation and induces apoptosis in human tumor cells. Oncogene 23, 5843–5852 (2004). https://doi.org/10.1038/sj.onc.1207757

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207757

Keywords

This article is cited by

Search

Quick links