Skip to main content
Log in

The neuronal pentraxin II gene (NPTX2) inhibit proliferation and invasion of pancreatic cancer cells in vitro

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The neuronal pentraxin II gene (NPTX2) is expressed in numerous tissues, such as the pancreas and the liver. While its activity in the brain is known to be regulated by neuronal activity, its function in the pancreas is unclear. In this study, we investigated the impact of NPTX2 on the proliferation, migration, invasion, apoptosis, and cell cycle of the pancreatic cancer cells. The expression levels of NPTX2 and their relation to the methylation level of the NPTX2 gene promoter in five pancreatic cancer cell lines were observed. The lower expression of NPTX2 in the cells was restored after the treatment of DNA methyltransferase inhibitor (5-aza-2′-deoxycytidine). Additionally, a full-length NPTX2 cDNA was transfected into pancreatic cancer cells (PANC-1) and we obtained the stably transfected cells (PANC-1-NPTX2). The ectopic NPTX2 expression significantly promoted G0-G1 arrest and cell apoptosis, and reduced cell proliferation, migration and invasion. Notably, the pro-apoptotic gene bax expression was significantly up-regulated while pro-survival gene bcl-2 did not significantly change in the stably transfected cells. Meanwhile, Cyclin D1 was significantly down-regulated. This study suggests that NPTX2, as a tumor-suppressor, plays an anti-tumor effect on pancreatic cancer and its low expression, due to promoter hypermethylation, may play a role in the tumorigenesis of pancreatic cancer.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Hruban R, Iacobuzio-Donahue C, Goggins M, Wilentz RE, Kern S (2001) Molecular pathology of pancreatic cancer. Cancer J 7:251–258

    PubMed  CAS  Google Scholar 

  2. Gao J, Li Z, Chen Z, Shao J, Zhang L, Xu G, Tu Z, Gong Y (2006) Antisense Smo under the control of the PTCH1 promoter delivered by an adenoviral vector inhibits the growth of human pancreatic cancer. Gene Ther 13:1587–1594

    Article  PubMed  CAS  Google Scholar 

  3. Zhang J, Zhang X, Zhu Y, Chen Z, Xu Z, Miao Y (2010) Transcriptional regulation of human mucin gene MUC4 in pancreatic cancer cells. Mol Biol Rep 37:2797–2802

    Article  PubMed  CAS  Google Scholar 

  4. Kurer MA (2007) Protein and mRNA expression of tissue factor pathway inhibitor-1 (TFPI-1) in breast, pancreatic and colorectal cancer cells. Mol Biol Rep 34:221–224

    Article  PubMed  CAS  Google Scholar 

  5. Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429:457–463

    Article  PubMed  CAS  Google Scholar 

  6. Noyer-Weidner M, Trautner TA (1993) Methylation of DNA in prokaryotes. EXS 64:39–108

    PubMed  CAS  Google Scholar 

  7. Colot V, Rossignol JL (1999) Eukaryotic DNA methylation as an evolutionary device. Bioessays 21:402–411

    Article  PubMed  CAS  Google Scholar 

  8. Baylin SB, Herman JG (2000) DNA hypermethylation in tumorigenesis: epigenetics joins genetics. Trends Genet 16:168–174

    Article  PubMed  CAS  Google Scholar 

  9. Hossain MA, Russell JC, O’Brien R, Laterra J (2004) Neuronal pentraxin 1: a novel mediator of hypoxic-ischemic injury in neonatal brain. J Neurosci 24:4187–4196

    Article  PubMed  CAS  Google Scholar 

  10. Bjartmar L, Huberman AD, Ullian EM, Rentería RC, Liu X, Xu W, Prezioso J, Susman MW, Stellwagen D, Stokes CC, Cho R, Worley P, Malenka RC (2006) Neuronal pentraxins mediate synaptic refinement in the developing visual system. J Neurosci 26:6269–6281

    Article  PubMed  CAS  Google Scholar 

  11. Tsui CC, Copeland NG, Gilbert DJ, Jenkins NA, Barnes C, Worley PF (1996) Narp, a novel member of the pentraxin family, promotes neurite outgrowth and is dynamically regulated by neuronal activity. J Neurosci 16:2463–2478

    PubMed  CAS  Google Scholar 

  12. Hsu YC, Perin MS (1995) Human neuronal pentraxin II (NPTX2): conservation, genomic structure, and chromosomal localization. Genomics 28:220–227

    Article  PubMed  CAS  Google Scholar 

  13. Sato N, Fukushima N, Maitra A, Matsubayashi H, Yeo CJ, Cameron JL, Hruban RH, Goggins M (2003) Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays. Cancer Res 63:3735–3742

    PubMed  CAS  Google Scholar 

  14. Matsubayashi H, Canto M, Sato N, Klein A, Abe T, Yamashita K, Yeo C, Kalloo A, Hruban R, Goggins M (2006) DNA methylation alterations in the pancreatic juice of patients with suspected pancreatic disease. Cancer Res 66:1208–1217

    Article  PubMed  CAS  Google Scholar 

  15. Park J, Ryu J, Lee K, Lee J, Yoon W, Lee S, Yoo J, Woo S, Lee G, Lee C, Kim Y, Yoon Y (2007) Quantitative analysis of NPTX2 hypermethylation is a promising molecular diagnostic marker for pancreatic cancer. Pancreas 35:e9–15

    Article  PubMed  Google Scholar 

  16. Eads CA, Danenberg KD, Kawakami K, Saltz LB, Blake C, Shibata D, Danenberg PV, Laird PW (2000) MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res 28:E32

    Article  PubMed  CAS  Google Scholar 

  17. Gao CL, Zhao DY, Qiu J, Zhang CM, Ji CB, Chen XH, Liu F, Guo XR (2009) Resistin induces rat insulinoma cell RINm5F apoptosis. Mol Biol Rep 36:1703–1708

    Article  PubMed  CAS  Google Scholar 

  18. Shridhar R, Zhang J, Song J, Booth BA, Kevil CG, Sotiropoulou G, Sloane BF, Keppler D (2004) Cystatin M suppresses the malignant phenotype of human MDA-MB-435S cells. Oncogene 23:10

    Article  Google Scholar 

  19. Zhang L, Huang H, Wu K, Wang M, Wu B (2010) Impact of BTG2 expression on proliferation and invasion of gastric cancer cells in vitro. Mol Biol Rep 37:2579–2586

    Article  PubMed  CAS  Google Scholar 

  20. Albo D, Tuszynski GP (2004) Thrombospondin-1 up-regulates tumor cell invasion through the urokinase plasminogen activator receptor in head and neck cancer cells. J Surg Res 120:21–26

    Article  PubMed  CAS  Google Scholar 

  21. Sato N, Fukushima N, Matsubayashi H, Goggins M (2004) Identification of maspin and S100P as novel hypomethylation targets in pancreatic cancer using global gene expression profiling. Oncogene 23:1531–1538

    Article  PubMed  CAS  Google Scholar 

  22. Ji L, Chena Y, Liua T, Wang ZT (2008) Involvement of Bcl-xL degradation and mitochondrial-mediated apoptotic pathway in pyrrolizidine alkaloids-induced apoptosis in hepatocytes. Toxicol Appl Pharmacol 231:393–400

    Article  PubMed  CAS  Google Scholar 

  23. Chang C, Zhu Y, Tang X, Tao W (2010) The anti-proliferative effects of norcantharidin on human HepG2 cells in cell culture. Mol Biol Rep

  24. Saeed S, Keehn CA, Khalil FK, Morgan MB (2005) Immunohistochemical expression of Bax and Bcl-2 in penile carcinoma. Ann Clin Lab Sci 35:91–96

    PubMed  CAS  Google Scholar 

  25. Miyashita T, Reed JC (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80:293–299

    Article  PubMed  CAS  Google Scholar 

  26. Santra MK, Wajapeyee N, Green MR (2009) F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage. Nature 459:722–725

    Article  PubMed  CAS  Google Scholar 

  27. Muller H, Lukas J, Schneider A, Warthoe P, Bartek J, Eilers M, Strauss M (1994) Cyclin D1 expression is regulated by the retinoblastoma protein. Proc Natl Acad Sci USA 91:2945–2949

    Article  PubMed  CAS  Google Scholar 

  28. Brisken C, Ayyannan A, Nguyen C, Heineman A, Reinhardt F, Tan J, Dey SK, Dotto GP, Weinberg RA (2002) IGF-2 is a mediator of prolactin-induced morphogenesis in the breast. Dev Cell 3:877–887

    Article  PubMed  CAS  Google Scholar 

  29. Toyoda M, Shirato H, Nakajima K, Kojima M, Takahashi M, Kubota M, Suzuki-Migishima R, Motegi Y, Yokoyama M, Takeuchi T (2003) Jumonji downregulates cardiac cell proliferation by repressing cyclin D1 expression. Dev Cell 5:85–97

    Article  PubMed  CAS  Google Scholar 

  30. Tetsu O, McCormick F (1999) Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:422–426

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Key Technology R&D Program of China (2006BAI02A12).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zhaoshen Li.

Additional information

Ling Zhang, Jun Gao, and Lei Li contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, L., Gao, J., Li, L. et al. The neuronal pentraxin II gene (NPTX2) inhibit proliferation and invasion of pancreatic cancer cells in vitro. Mol Biol Rep 38, 4903–4911 (2011). https://doi.org/10.1007/s11033-010-0632-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-010-0632-y

Keywords

Navigation