Skip to main content

Advertisement

Log in

Midkine mRNA Is Overexpressed in Pancreatic Cancer

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Purpose Midkine (MK) has been reported to be a possible molecular marker for the diagnosis of pancreatic cancer. We investigated the feasibility of quantitative analysis of MK mRNA by quantitative real-time RT-PCR (qRT-PCR) as a promising tool for the diagnosis of pancreatic cancer. Results We found that pancreatic cancer tissues expressed significantly higher levels of MK mRNA than intraductal pancreatic mucinous neoplasm (IPMN) and non-neoplastic pancreatic tissues (P < 0.05); in contrast, we did not find any differences in MK mRNA expression between IPMN and non-neoplastic pancreatic tissues. Additionally, we observed that poorly differentiated carcinoma samples expressed higher levels of MK mRNA than well-differentiated carcinoma samples, although a significant difference was not observed. Conclusions The present data suggests that quantitative analysis of MK mRNA provides an objective and sensitive evaluation and may be a promising modality for the diagnosis of pancreatic cancer and the prediction of its prognosis.

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

Similar content being viewed by others

References

  1. Li D, Xie K, Wolff R, Abbruzzese JL (2004) Pancreatic cancer. Lancet 363:1049–1057. doi:10.1016/S0140-6736(04)15841-8

    Article  PubMed  CAS  Google Scholar 

  2. Kadomatsu K, Tomomura M, Muramatsu T (1988) cDNA cloning and sequencing of a new gene intensely expressed in early differentiation stages of embryonal carcinoma cells and in mid-gestation period of mouse embryogenesis. Biochem Biophys Res Commun 151:1312–1318. doi:10.1016/S0006-291X(88)80505-9

    Article  PubMed  CAS  Google Scholar 

  3. Muramatsu H, Muramatsu T (1991) Purification of recombinant midkine and examination of its biological activities: functional comparison of new heparin binding factors. Biochem Biophys Res Commun 177:652–658. doi:10.1016/0006-291X(91)91838-4

    Article  PubMed  CAS  Google Scholar 

  4. Unoki K, Ohba N, Arimura H, Muramatsu H, Muramatsu T (1994) Rescue of photoreceptors from the damaging effects of constant light by midkine, a retinoic acid-responsive gene product. Invest Ophthalmol Vis Sci 35:4063–4068

    PubMed  CAS  Google Scholar 

  5. Choudhuri R, Zhang HT, Donnini S, Ziche M, Bicknell R (1997) An angiogenic role for the neurokines midkine and pleiotrophin in tumorigenesis. Cancer Res 57:1814–1819

    PubMed  CAS  Google Scholar 

  6. Kojima S, Muramatsu H, Amanuma H, Muramatsu T (1995) Midkine enhances fibrinolytic activity of bovine endothelial cells. J Biol Chem 270:9590–9596. doi:10.1074/jbc.270.16.9590

    Article  PubMed  CAS  Google Scholar 

  7. Qi M, Ikematsu S, Ichihara-Tanaka K, Sakuma S, Muramatsu T, Kadomatsu K (2000) Midkine rescues Wilms’ tumor cells from cisplatin-induced apoptosis: regulation of Bcl-2 expression by Midkine. J Biochem 127:269–277

    PubMed  CAS  Google Scholar 

  8. Owada K, Sanjo N, Kobayashi T et al (1999) Midkine inhibits caspase-dependent apoptosis via the activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase in cultured neurons. J Neurochem 73:2084–2092

    PubMed  CAS  Google Scholar 

  9. Kadomatsu K, Muramatsu T (2004) Midkine and pleiotrophin in neural development and cancer. Cancer Lett 204:127–143. doi:10.1016/S0304-3835(03)00450-6

    Article  PubMed  CAS  Google Scholar 

  10. Tsutsui J, Kadomatsu K, Matsubara S et al (1993) A new family of heparin-binding growth/differentiation factors: increased midkine expression in Wilms’ tumor and other human carcinomas. Cancer Res 53:1281–1285

    PubMed  CAS  Google Scholar 

  11. Miyashiro I, Kaname T, Shin E et al (1997) Midkine expression in human breast cancers: expression of truncated form. Breast Cancer Res Treat 43:1–6. doi:10.1023/A:1005748728351

    Article  PubMed  CAS  Google Scholar 

  12. Aridome K, Takao S, Kaname T et al (1998) Truncated midkine as a marker of diagnosis and detection of nodal metastases in gastrointestinal carcinomas. Br J Cancer 78:472–477

    PubMed  CAS  Google Scholar 

  13. Ye C, Qi M, Fan QW et al (1999) Expression of midkine in the early stage of carcinogenesis in human colorectal cancer. Br J Cancer 79:179–184. doi:10.1038/sj.bjc.6690030

    Article  PubMed  CAS  Google Scholar 

  14. O’Brien T, Cranston D, Fuggle S, Bicknell R, Harris AL (1996) The angiogenic factor midkine is expressed in bladder cancer, and overexpression correlates with a poor outcome in patients with invasive cancers. Cancer Res 56:2515–2518

    PubMed  CAS  Google Scholar 

  15. Kaname T, Kadomatsu K, Aridome K et al (1996) The expression of truncated MK in human tumors. Biochem Biophys Res Commun 219:256–260. doi:10.1006/bbrc.1996.0214

    Article  PubMed  CAS  Google Scholar 

  16. Maeda S, Shinchi H, Kurahara H et al (2007) Clinical significance of midkine expression in pancreatic head carcinoma. Br J Cancer 97:405–411. doi:10.1038/sj.bjc.6603879

    Article  PubMed  CAS  Google Scholar 

  17. Ohuchida K, Mizumoto K, Ishikawa N et al (2005) The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target. Clin Cancer Res 11:7785–7793. doi:10.1158/1078-0432.CCR-05-0714

    Article  PubMed  CAS  Google Scholar 

  18. Ruan M, Ji T, Wu Z, Zhou J, Zhang C (2007) Evaluation of expression of midkine in oral squamous cell carcinoma and its correlation with tumour angiogenesis. Int J Oral Maxillofac Surg 36:159–164. doi:10.1016/j.ijom.2006.09.004

    Article  PubMed  CAS  Google Scholar 

  19. Moon HS, Park WI, Sung SH, Choi EA, Chung HW, Woo BH (2003) Immunohistochemical and quantitative competitive PCR analyses of midkine and pleiotrophin expression in cervical cancer. Gynecol Oncol 88:289–297. doi:10.1016/S0090-8258(02)00070-7

    Article  PubMed  CAS  Google Scholar 

  20. Shimada H, Nabeya Y, Tagawa M et al (2003) Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma. Cancer Sci 94:628–632. doi:10.1111/j.1349-7006.2003.tb01494.x

    Article  PubMed  CAS  Google Scholar 

  21. Obata Y, Kikuchi S, Lin Y, Yagyu K, Muramatsu T, Kumai H (2005) Serum midkine concentrations and gastric cancer. Cancer Sci 96:54–56

    PubMed  CAS  Google Scholar 

  22. Ohuchida K, Mizumoto K, Yamada D et al (2006) Quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice for preoperative diagnosis of pancreatic cancer. Int J Cancer 118:405–411. doi:10.1002/ijc.21317

    Article  PubMed  CAS  Google Scholar 

  23. Wiesenauer CA, Schmidt CM, Cummings OW et al (2003) Preoperative predictors of malignancy in pancreatic intraductal papillary mucinous neoplasms. Arch Surg 138:610–617. doi:10.1001/archsurg.138.6.610 discussion 7–8

    Article  PubMed  Google Scholar 

  24. Rodallec M, Vilgrain V, Couvelard A et al (2006) Endocrine pancreatic tumours and helical CT: contrast enhancement is correlated with microvascular density, histoprognostic factors and survival. Pancreatology 6:77–85. doi:10.1159/000090026

    Article  PubMed  CAS  Google Scholar 

  25. Chatelain D, Flejou JF (2002) Pancreatectomy for adenocarcinoma: prognostic factors, recommendations for pathological reports. Ann pathol 22:422–431

    PubMed  Google Scholar 

Download references

Acknowledgments

This research work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and grants from the Fukuoka Cancer Society and Kaibara Morikazu Medical Science Promotion Foundation. We are grateful to Emiko Manabe, Makiko Masuda, and Miyuki Omori (Department of Surgery and Oncology, Kyushu University) for skillful technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kenoki Ohuchida.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ohhashi, S., Ohuchida, K., Mizumoto, K. et al. Midkine mRNA Is Overexpressed in Pancreatic Cancer. Dig Dis Sci 54, 811–815 (2009). https://doi.org/10.1007/s10620-008-0434-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-008-0434-4

Keywords

Navigation