Skip to main content

Advertisement

SpringerLink
Log in

Expression of MT2 Receptor in Patients with Gastric Adenocarcinoma and its Relationship with Clinicopathological Features

  • Original Research
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Background

Gastric cancer accounts 8 % of the total cancer cases and 10 % of total cancer deaths worldwide. The indoleamine N-acetyl-5-methoxytryptamine, better known as melatonin, is the principal hormone produced by the pineal gland. Recently, it has shown some anticancer role in some malignancies such as breast and colon cancer; also, some of its protective roles in the GI tract are as free radical scavenger and as antimitogenic and apoptotic agents. Based on the anticancer effects of melatonin and wide distribution of this neurohormone in the GI tract and some proposed physiologic and pharmacologic roles for this neurohormone, this study is initially scheduled to determine the expression of melatonin receptor MT2 in tissue samples of adenocarcinoma cancer patients.

Methods

For this aim, a total of 30 gastric adenocarcinoma patients and 30 normal individuals were selected and examined for MT2 gene expression by real-time PCR.

Results

Our results have shown interestingly high expression for MT2 receptor in cancer and marginal cancer tissues compared with normal people.

Conclusions

According to our results, it is concluded that for the first time, the expression of MT2 receptor in gastric adenocarcinoma tissues which was in parallel with breast and colon cancer studies and high expression of this receptor in the marginal tissues indicate refractory mechanism which shows the defending role of melatonin in the GI system. Our experiments has not shown any relationship between MT2 receptor expression and grade and clinicopathological features of gastric tumor, so we cannot conclude any relationship between this receptor expression and progression of the tumor, although this expression can be considered as an etiology.

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
Fig. 5

Similar content being viewed by others

References

  1. Parkin D et al. Global cancer statistics. CA Cancer J. 2002;55:74–108.

    Article  Google Scholar 

  2. Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. European Journal of Cancer. 37. Supplement. 2001;8:4–66.

    Google Scholar 

  3. Axon A. Symptoms and diagnosis of gastric cancer at early curable stage. Best Pract Res Clin Gastroenterol. 2006;20(4):697–708.

    Article  PubMed  Google Scholar 

  4. Pinto E, Roviello F, Stefano A. Early gastric cancer: report on 142 patients observed over 13 years. Jpn J Clin Oncol. 1994;24:12–9.

    CAS  PubMed  Google Scholar 

  5. Sung N et al. Smoking, alcohol and gastric cancer risk in Korean men: the National Health Insurance Corporation Study. Br J Cancer. 2007;97(5):700–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. WHO, Initiative for Vaccine Research team of the Department of Immunization, Vaccines and Biologicals. Epidemiology of Helicobacter pylori and gastric cancer. In Proceedings of the Fourth Global Vaccine Research Forum. 2004

  7. Underwood H, Goldman B. Vertebrate circadian and photoperiodic systems: role of the pineal gland and melatonin. J Biol Rhythms. 1987;5:279–315.

    Article  Google Scholar 

  8. Pardridge V. Transport of protein-bound hormones into tissues in vivo. Endocr. 1981;2(1):103–23.

    Article  CAS  Google Scholar 

  9. Yu H, Reiter R. Melatonin: biosynthesis, physiological effects, and clinical applications. Boca Raton: CRC; 1993.

    Google Scholar 

  10. Pandi-Perumal SR et al. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol. 2008;85(3):335–53.

    Article  CAS  PubMed  Google Scholar 

  11. Stefulj J et al. Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat. J Pineal Res. 2001;30:243–7.

    Article  CAS  PubMed  Google Scholar 

  12. Fiske V et al. Effect of melatonin alone or in combination with human chorionic gonadotropin or ovine luteinizing hormone on the in vitro secretion of estrogens or progesterone by granulosa cells of rats. Endocrinology. 1984;114:407–10.

    Article  CAS  PubMed  Google Scholar 

  13. Brzezinski A. Melatonin in humans. N Engl J. 1997;336(3):186–95.

    Article  CAS  Google Scholar 

  14. Cos S et al. Melatonin as a selective estrogen enzyme modulator. Curr Cancer Drug Targets. 2008;8(8):691–702.

    Article  CAS  PubMed  Google Scholar 

  15. Ekmekcioglu C. Melatonin receptors in humans: biological role and clinical relevance. Biomed Pharmacother. 2006;60(3):97–108.

    Article  CAS  PubMed  Google Scholar 

  16. Reiter RJ et al. Medical implications of melatonin: receptor-mediated and receptor-independent actions. Adv Med Sci. 2007;52:11–28.

    CAS  PubMed  Google Scholar 

  17. Boutin JA et al. Molecular tools to study melatonin pathways and actions. Trends Pharmacol Sci. 2005;26(8):412–9.

    Article  CAS  PubMed  Google Scholar 

  18. Hardeland R. Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine. 2005;27(2):119–30.

    Article  CAS  PubMed  Google Scholar 

  19. Reiter RJ, Manchester L, Tan DX. Neurotoxins: free radical mechanisms and melatonin protection. Curr Neuropharmacol. 2010;8(3):194–210.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Arnao and Hernandez-Ruiz, 2006. The physiological function of melatonin in plants. Landes Bioscience. p. 2012–13

  21. Poeggeler B et al. Melatonin–a highly potent endogenous radical scavenger and electron donor: new aspects of the oxidation chemistry of this indole accessed in vitro. Ann N Y Acad Sci. 1994;738:419–20.

    Article  CAS  PubMed  Google Scholar 

  22. Reppert, S., D. Weaver, and E. T, 1994. Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. 13:1177–85.

  23. Reppert S et al. Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proc Natl Acad Sci U S A. 1995;92:8734–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Coughlin CC et al. Effect of marked weight loss on adiponectin gene expression and plasma concentrations. Obesity. 2007;15(3):640–5.

    Article  CAS  PubMed  Google Scholar 

  25. Rivara S et al. Melatonin receptor agonists: SAR and application to the treatment of sleep-wake disorders. Curr Top Med Chem. 2008;11(8):954–68.

    Article  Google Scholar 

  26. Sugden D et al. Melatonin, melatonin receptors and melanophores. Pigment Cell Res. 2004;17(5):454–60.

    Article  CAS  PubMed  Google Scholar 

  27. Dubocovich ML et al. International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol Rev. 2010;62(3):343–80.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Roca AL et al. Structure, characterization and expression of the gene encoding the mouse Mel1a melatonin receptor. Endocrinology. 1996;137:3469–77.

    CAS  PubMed  Google Scholar 

  29. Slominski A et al. On the role of melatonin in skin physiology and pathology. Endocrine. 2005;27:137–48.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Konturek SJ, Konturek PC, Brzozowski T. Melatonin in gastroprotection against stress-induced acute gastric lesions and in healing of chronic gastric ulcers. J Physiol Pharmacol. 2006;57:51–66.

    Google Scholar 

  31. Dubocovich ML, Markowska. Functional MT1 and MT2 melatonin receptors in mammals. Endocrine. 2005;27:101–10.

    Article  CAS  PubMed  Google Scholar 

  32. Lanoix D et al. Expression of melatoninergic receptors in human placental choriocarcinoma cell lines. Hum Reprod. 2006;21:1981–9.

    Article  CAS  PubMed  Google Scholar 

  33. Karasek M et al. Expression of melatonin MT(1) and MT(2) receptors, and ROR alpha(1) receptor in transplantable murine Colon 38 cancer. Neuro Endocrinol Lett. 2002;1:55–60.

    Google Scholar 

  34. Oprea-Ilies G et al. 2013, Expression of melatonin receptors in triple negative breast cancer (TNBC) in African American and Caucasian women: relation to survival. 137;677–687.

  35. Qiagen. RNeasy ® Plus Mini Handbook. Limburg: Qiagen; 2010.

    Google Scholar 

  36. Mowla S et al. Evaluating expression and potential diagnostic and prognostic values of survivin in bladder tumors: a preliminary report. Urol J. 2005;2:141–7.

    PubMed  Google Scholar 

  37. Mistry T. Leptin and adiponectin interact in the regulation of prostate cancer cell growth via modulation of p53 and bcl2 expression. BJU Int. 2008;101(10):1317–22.

    Article  CAS  PubMed  Google Scholar 

  38. Behjati F et al. Prognostic value of chromosome 1 and 8 copy number in invasive ductal breast carcinoma among Iranian women. Pathol Oncol Res. 2005;11(3):157–63.

    Article  PubMed  Google Scholar 

  39. Barni S, Lissoni P, Crispino S. Neouroimmunomodulation in cancer patients: correlation between melatonin and beta-endorphin blood levels and T-helper/suppressor ratio. J Biol Markers. 1988;3:82–6.

    CAS  Google Scholar 

  40. Cois S et al. Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells. Cancer Res. 1998;58:4383–90.

    Google Scholar 

  41. Radomir M et al. Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol Cell Endocrinol. 2012;351:152–66.

    Article  Google Scholar 

  42. Lanoix D, Ouelette R, Vaillancourt C. Expression of melatoninergic receptors in human placental choriocarcinoma cell line. Hum Reprod. 2006;21:1981–89.

    Article  CAS  PubMed  Google Scholar 

  43. Pandi-perumal, S., s. V, and G. Maestroni, 2006. Melatonin: nature's most versatile biological signal? FEBS J. 273; 2813–2838.

  44. González A et al. Effects of MT1 melatonin receptor overexpression on the aromatase-suppressive effect of melatonin in MCF-7 human breast cancer cells. Oncol Rep. 2007;17:947–53.

    PubMed  Google Scholar 

  45. Yuan L et al. MT(1) melatonin receptor overexpression enhances the growth suppressive effect of melatonin in human breast cancer cells. Mol Cell Endocrinol. 2002;192:147–56.

    Article  CAS  PubMed  Google Scholar 

  46. Collins A et al. Over-expression of the MT1 melatonin receptor in MCF-7 human breast cancer cells inhibits mammary tumor formation in nude mice. Cancer Lett. 2003;189:49–57.

    Article  CAS  PubMed  Google Scholar 

  47. Quastel MR, Rahamimoff R. Effect of melatonin on spontaneous contractions and response to 5-hydroxytryptamine of rat isolated duodenum. Br Pharmacol Chemother. 1995;24:455–61.

    Article  Google Scholar 

  48. Rodriguez C et al. Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res. 2004;36:1–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge Dr. Zarbackt Ansari from the Agricultural Sciences faculty of Mazandaran University for providing some facilities necessary to carry out our research work and for his nice collaboration.

Author information

Authors and Affiliations

  1. Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Nafiseh Nasri Nasrabadi, Ramin Ataee, Mohammad Shokrzadeh & Hamed Haghi Amin Jan

  2. Thalassemia Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Ramin Ataee

  3. Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Saeid Abediankenari

  4. Mazandaran University of Agriculture Sciences and Natural Resources, Sari, Iran

    Mojtaba Najafi

  5. Gastroenterology Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Seyed Vahid Hoseini

Authors
  1. Nafiseh Nasri Nasrabadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ramin Ataee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Saeid Abediankenari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohammad Shokrzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mojtaba Najafi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Seyed Vahid Hoseini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hamed Haghi Amin Jan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ramin Ataee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nasrabadi, N.N., Ataee, R., Abediankenari, S. et al. Expression of MT2 Receptor in Patients with Gastric Adenocarcinoma and its Relationship with Clinicopathological Features. J Gastrointest Canc 45, 54–60 (2014). https://doi.org/10.1007/s12029-013-9552-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-013-9552-0

Keywords

Search

Navigation