Skip to main content

Advertisement

SpringerLink
Log in

The nucleosome binding protein NSBP1 is highly expressed in human bladder cancer and promotes the proliferation and invasion of bladder cancer cells

  • Research Article
  • Published:
Tumor Biology

Abstract

NSBP1 is a recently identified member of the HMGN protein family which binds to nucleosomes and regulates gene transcription through chromatin remodeling. In this study, we aimed to investigate the potential role of NSBP1 in human bladder cancer. We examined NSBP1 expression in 114 surgically removed bladder cancer specimens as well as 11 human bladder cell lines by immunohistochemistry and Western blot analysis, and found that NSBP1 level was correlated with the increased tumor grade and pathologic stage, and lymph node metastasis. RNAi-mediated knockdown of NSBP1 in EJ cells, a bladder cancer cell line that overexpressed NSBP1, resulted in moderate decrease of cell viability, moderate blockage of cell cycle at G2/M phase, and decreased cyclin B1 expression, but had no effects on apoptosis. Moreover, NSBP1 knockdown led to reduced activity of MMP-9 but not MMP-2. Taken together, these results suggest that NSBP1 promotes the viability of bladder cancer cells through increased cell proliferation but not decreased apoptosis, and increases the invasion ability of metastatic bladder cancer cells through the upregulation of MMP-9 activity. Our findings not only provide a molecular understanding of the role of NSBP1 in bladder cancer, but also suggest NSBP1 RNAi as a novel therapeutic approach for bladder cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

HMGs:

High mobility group proteins

NBD:

Nucleosomal binding domain

NSBP1:

Nucleosomal binding protein 1

SDS-PAGE:

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis

MMPs:

Matrix metallopeptidases

NLS:

Nuclear localization signal

References

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.

    Article  PubMed  Google Scholar 

  2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59(4):225–49.

    Article  PubMed  Google Scholar 

  3. Fangliu G, Yuli L. Changing status of genitourinary cancer in recent 50 years. Chin J Urol. 2002;23(2):88–90.

    Google Scholar 

  4. Kuo MH, Allis CD. Roles of histone acetyltransferases and deacetylases in gene regulation. Bioessays. 1998;20(8):615–26.

    Article  PubMed  CAS  Google Scholar 

  5. Brown CE, Lechner T, Howe L, Workman JL. The many HATs of transcription coactivators. Trends Biochem Sci. 2000;25(1):15–9.

    Article  PubMed  CAS  Google Scholar 

  6. Cheung P, Allis CD, Sassone-Corsi P. Signaling to chromatin through histone modifications. Cell. 2000;103(2):263–71.

    Article  PubMed  CAS  Google Scholar 

  7. Ng HH, Bird A. Histone deacetylases: silencers for hire. Trends Biochem Sci. 2000;25(3):121–6.

    Article  PubMed  CAS  Google Scholar 

  8. Bird AP, Wolffe AP. Methylation-induced repression—belts, braces, and chromatin. Cell. 1999;99(5):451–4.

    Article  PubMed  CAS  Google Scholar 

  9. Kornberg RD, Lorch Y. Chromatin-modifying and -remodeling complexes. Curr Opin Genet Dev. 1999;9(2):148–51.

    Article  PubMed  CAS  Google Scholar 

  10. Vignali M, Hassan AH, Neely KE, Workman JL. ATP-dependent chromatin-remodeling complexes. Mol Cell Biol. 2000;20(6):1899–910.

    Article  PubMed  CAS  Google Scholar 

  11. Bustin M, Reeves R. High-mobility-group chromosomal proteins: architectural components that facilitate chromatin function. Prog Nucleic Acid Res Mol Biol. 1996;54:35–100.

    Article  PubMed  CAS  Google Scholar 

  12. Bustin M. Regulation of DNA-dependent activities by the functional motifs of the high-mobility-group chromosomal proteins. Mol Cell Biol. 1999;19(8):5237–46.

    PubMed  CAS  Google Scholar 

  13. Bianchi ME, Agresti A. HMG proteins: dynamic players in gene regulation and differentiation. Curr Opin Genet Dev. 2005;15(5):496–506.

    Article  PubMed  CAS  Google Scholar 

  14. Fusco A, Fedele M. Roles of HMGA proteins in cancer. Nat Rev Cancer. 2007;7(12):899–910.

    Article  PubMed  CAS  Google Scholar 

  15. Hock R, Furusawa T, Ueda T, Bustin M. HMG chromosomal proteins in development and disease. Trends Cell Biol. 2007;17(2):72–9.

    Article  PubMed  CAS  Google Scholar 

  16. Birger Y, Ito Y, West KL, Landsman D, Bustin M. HMGN4, a newly discovered nucleosome-binding protein encoded by an intronless gene. DNA Cell Biol. 2001;20(5):257–64.

    Article  PubMed  CAS  Google Scholar 

  17. West KL, Ito Y, Birger Y, Postnikov Y, Shirakawa H, Bustin M. HMGN3a and HMGN3b, two protein isoforms with a tissue-specific expression pattern, expand the cellular repertoire of nucleosome-binding proteins. J Biol Chem. 2001;276(28):25959–69.

    Article  PubMed  CAS  Google Scholar 

  18. Shirakawa H, Landsman D, Postnikov YV, Bustin M. NBP-45, a novel nucleosomal binding protein with a tissue-specific and developmentally regulated expression. J Biol Chem. 2000;275(9):6368–74.

    Article  PubMed  CAS  Google Scholar 

  19. King LM, Francomano CA. Characterization of a human gene encoding nucleosomal binding protein NSBP1. Genomics. 2001;71(2):163–73.

    Article  PubMed  CAS  Google Scholar 

  20. Rochman M, Postnikov Y, Correll S, Malicet C, Wincovitch S, Karpova TS, et al. The interaction of NSBP1/HMGN5 with nucleosomes in euchromatin counteracts linker histone-mediated chromatin compaction and modulates transcription. Mol Cell. 2009;35(5):642–56.

    Article  PubMed  CAS  Google Scholar 

  21. Zhou LQ, Song G, He ZS, Hao JR, Na YQ. Effects of inhibiting nucleosomal binding protein 1 on proliferation of human prostate cancer cells. Zhonghua Yi Xue Za Zhi. 2007;87(6):404–8.

    PubMed  CAS  Google Scholar 

  22. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001;25(4):402–8.

    Article  PubMed  CAS  Google Scholar 

  23. Sherr CJ, Roberts JM. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 1995;9(10):1149–63.

    Article  PubMed  CAS  Google Scholar 

  24. Pines J, Hunter T. Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport. J Cell Biol. 1991;115(1):1–17.

    Article  PubMed  CAS  Google Scholar 

  25. Moldovan GL, Pfander B, Jentsch S. PCNA, the maestro of the replication fork. Cell. 2007;129(4):665–79.

    Article  PubMed  CAS  Google Scholar 

  26. Aizawa K, Ueki K, Suzuki S, Yabusaki H, Kanda T, Nishimaki T, et al. Apoptosis and Bcl-2 expression in gastric carcinomas: correlation withclinicopathological variables, p53 expression, cell proliferation and prognosis. Int J Oncol. 1999;14(1):85–91.

    PubMed  CAS  Google Scholar 

  27. Shirakawa H, Rochman M, Furusawa T, Kuehn MR, Horigome S, Haketa K, et al. The nucleosomal binding protein NSBP1 is highly expressed in the placenta and modulates the expression of differentiation markers in placental Rcho-1 cells. J Cell Biochem. 2009;106(4):651–8.

    Article  PubMed  CAS  Google Scholar 

  28. Huang C, Zhou LQ, Song G. Effect of nucleosomal binding protein 1 in androgen-independent prostatic carcinoma. Zhonghua Yi Xue Za Zhi. 2008;88(10):657–60.

    PubMed  CAS  Google Scholar 

  29. Jiang N, Zhou LQ, Zhang XY. Downregulation of the nucleosome-binding protein 1 (NSBP1) gene can inhibit the in vitro and in vivo proliferation of prostate cancer cells. Asian J Androl. 2010;12(5):709–17.

    Article  PubMed  CAS  Google Scholar 

  30. Hamasaki T, Hattori T, Kimura G, Nakazawa N. Tumor progression and expression of matrix metalloproteinase-2 (MMP-2) mRNA by human urinary bladder cancer cells. Urol Res. 1998;26(6):371–6.

    Article  PubMed  CAS  Google Scholar 

  31. Hanemaaijer R, Sier CF, Visser H, Scholte L, van Lent N, Toet K, et al. MMP-9 activity in urine from patients with various tumors, as measured by a novel MMP activity assay using modified urokinase as a substrate. Ann NY Acad Sci. 1999;878:141–9.

    Article  PubMed  CAS  Google Scholar 

  32. Belotti D, Paganoni P, Manenti L, Garofalo A, Marchini S, Taraboletti G, et al. Matrix metalloproteinases (MMP9 and MMP2) induce the release of vascular endothelial growth factor (VEGF) by ovarian carcinoma cells: implications for ascites formation. Cancer Res. 2003;63(17):5224–9.

    PubMed  CAS  Google Scholar 

  33. Huang S, Van Arsdall M, Tedjarati S, McCarty M, Wu W, Langley R, et al. Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. J Natl Cancer Inst. 2002;94(15):1134–42.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Prof. Ding-Fang Bu for his technical support and critical reading of this manuscript. This work was supported by grants from the National Natural Science Foundation of China (Nos. 30271295 and 30672099) and Beijing Natural Science Foundation (No. 7092101).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Urology, Peking University First Hospital, Beijing, China

    Wasilijiang Wahafu, Zhi-Song He, Xiao-Yu Zhang, Cui-Jian Zhang, Kun Yao, Han Hao, Gang Song, Qun He, Xue-Song Li & Li-Qun Zhou

  2. The Institute of Urology, Peking University, Beijing, China

    Wasilijiang Wahafu, Zhi-Song He, Xiao-Yu Zhang, Cui-Jian Zhang, Kun Yao, Han Hao, Gang Song, Qun He, Xue-Song Li & Li-Qun Zhou

  3. National Urological Cancer Center, Beijing, 100034, China

    Wasilijiang Wahafu, Zhi-Song He, Xiao-Yu Zhang, Cui-Jian Zhang, Kun Yao, Han Hao, Gang Song, Qun He, Xue-Song Li & Li-Qun Zhou

Authors
  1. Wasilijiang Wahafu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhi-Song He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao-Yu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cui-Jian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kun Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Han Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gang Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qun He
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xue-Song Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Li-Qun Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Li-Qun Zhou.

Additional information

Wasilijiang Wahafu and Zhi-Song He contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wahafu, W., He, ZS., Zhang, XY. et al. The nucleosome binding protein NSBP1 is highly expressed in human bladder cancer and promotes the proliferation and invasion of bladder cancer cells. Tumor Biol. 32, 931–939 (2011). https://doi.org/10.1007/s13277-011-0195-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-011-0195-0

Keywords

Search

Navigation