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Evaluation of Gene Expression Changes of Serotonin Receptors, 5-HT3AR and 5-HT2AR as Main Stress Factors in Breast Cancer Patients

  • Hejazi, Seyed Hesam (Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Iran University of Medical Sciences) ;
  • Ahangari, Ghasem (Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Iran University of Medical Sciences) ;
  • Pornour, Majid (Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Iran University of Medical Sciences) ;
  • Deezagi, Abdolkhaleagh (Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Iran University of Medical Sciences) ;
  • Aminzadeh, Saeed (Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Iran University of Medical Sciences) ;
  • Ahmadkhaniha, Hamid Reza (Department of Psychiatry, Mental Health Research Center, Iran University of Medical Sciences) ;
  • Akbari, Mohamad Esmail (Cancer Research Center, Shohada Hospital, Shahid Beheshti University of Medical Sciences)
  • Published : 2014.06.15

Abstract

Breast cancer is a serious and potentially lethal multi-factor disease among 40-50 aged women in both developed and developing countries. Also, various studies have pointed to roles of neurotransmitters like serotonin in development of cancers, through action on various types of receptors. This study was conducted to evaluate serotonin receptor (5HT2AR and 5HT3AR) genes expression in peripheral blood mononuclear cells (PBMCs) of breast cancer patients in comparison with the healthy people and in the MCF7 cell line. Peripheral blood samples were obtained from 30 patients and 30 healthy individuals. Total RNA was extracted from PBMCs and MCF-7 cells. and 5HT2AR and 5HT3AR were detected by RT-PCR techniques. Finally, serotonin receptor gene expression variation in breast cancer patients and MCF-7 cells were determined by real time-PCR. This latter indicated significant promotion in expression of 5HT3AR and 5HT2AR in PBMCs in breast cancer patients but expression of 5HT2AR in the MCF-7 cell line was significantly decreased. In conclusion, after performing complimentary tests, determine of gene expression changes in serotonin receptors (5HT2AR and 5HT3AR) may be useful as a new approach in treatment of breast cancer based on use of antagonists.

Acknowledgement

Supported by : National Institute of Genetic Engineering and Biotechnology(NIGEB), Cancer Research Center (CRC)

References

  1. Adayev T, Ray I, Sondhi R, Sobocki T, Banerjee P (2003). The gprotein-coupled 5-htr1a receptor causes suppression of caspase-3 through mapk and protein kinase c$\alpha$. BBA-Mol Cell Res, 1640, 85-96.
  2. Akbari A, Razzaghi Z, Homaee F, et al (2011). Parity and breastfeeding are preventive measures against breast cancer in iranian women. Breast Cancer, 18, 51-5. https://doi.org/10.1007/s12282-010-0203-z
  3. Antonova L, Aronson K, Mueller CR (2011). Stress and breast cancer: from epidemiology to molecular biology. Breast Cancer Res, 13, 208. https://doi.org/10.1186/bcr2836
  4. Aro AR, Koning HD, Schreck M, et al (2005). Psychological risk factors of incidence of breast cancer: a prospective cohort study in finland. Psychol Med, 35, 1515-21. https://doi.org/10.1017/S0033291705005313
  5. Cogolludo A, Moreno L, Lodi F, et al. (2006). Serotonin inhibits voltage-gated k+ currents in pulmonary artery smooth muscle cells role of 5-ht2a receptors, Caveolin-1, and KV1. 5 channel internalization. Circ Res, 98, 931-38. https://doi.org/10.1161/01.RES.0000216858.04599.e1
  6. Donegan WL, Redlich PN (1996). Breast cancer in men. Surg Clin North Am, 76, 343-63. https://doi.org/10.1016/S0039-6109(05)70443-6
  7. Haghighat S, Akbari M, Ghaffari S, Yavari P (2012). Standardized breast cancer mortality rate compared to the general female population of Iran. Asian Pac J Cancer Prev, 13, 5525-28. https://doi.org/10.7314/APJCP.2012.13.11.5525
  8. Hannon J, Hoyer D (2008). Molecular Biology of 5-HT receptors. Behav Brain Res, 195, 198-213. https://doi.org/10.1016/j.bbr.2008.03.020
  9. Khan NA, Hichami A (1999). Ionotrophic 5-hydroxytryptamine type 3 receptor activates the protein kinase c-dependent phospholipase d pathway in human T-cells. Biochem J, 344, 199-204 https://doi.org/10.1042/0264-6021:3440199
  10. Helmrich SP, Shapiro S, Rosenberg L, et al (1983). Risk factors for breast cancer. Am J Epidemiol, 117, 35-45.
  11. Herbert TB, Cohen S (1993). Depression and Immunity: A meta-analytic review. Psychol Bull, 113, 472-86. https://doi.org/10.1037/0033-2909.113.3.472
  12. Iken K, Chheng S, Fargin A, Goulet A-C, Kouassi E (1995). Serotonin upregulates mitogen-stimulated b lymphocyte proliferation through 5-ht1a receptors. Cell Immunol, 163, 1-9. https://doi.org/10.1006/cimm.1995.1092
  13. Kopparapu PK, Tinzl M, Anagnostaki L, Persson JL, Dizeyi, N (2013). Expression and localization of serotonin receptors in human breast cancer. Anticancer Res, 33, 363-70.
  14. Leonard BE (2010). The concept of depression as a dysfunction of the immune system. Curr Immunol Rev, 6, 205-212. https://doi.org/10.2174/157339510791823835
  15. Madigan MP, Ziegler RG, Benichou J, Byrne C, Hoover RN (1995). Proportion of breast cancer cases in the united states explained by well-established risk factors. J Natl Cancer Inst, 87, 1681-85. https://doi.org/10.1093/jnci/87.22.1681
  16. Moorman PG, Grubber JM, Millikan RC, Newman B (2003). Antidepressant medications and their association with invasive breast cancer and carcinoma in situ of the breast. Epidemiology, 14, 307-14.
  17. Nazlican E, Akbaba M, Okyay RA (2012). Evaluation of depression in newly diagnosed breast cancer cases in Hatay province of Turkey in 2011. Asian Pac J Cancer Prev, 13, 2557-61. https://doi.org/10.7314/APJCP.2012.13.6.2557
  18. Persky VW, Kempthorne-Rawson J, Shekelle RB (1987). Personality and risk of cancer: 20-year follow-up of the western electric study. Psychosom Med, 49, 435-49. https://doi.org/10.1097/00006842-198709000-00001
  19. Schoevers R, Beekman A, Van Tilburg W, et al. (2000). Association of depression and gender with mortality in old age results from the amsterdam study of the elderly (AMSTEL). Br J Psychiatry, 177, 336-42. https://doi.org/10.1192/bjp.177.4.336
  20. Pinquart M, Duberstein PR (2010). Depression and cancer mortality: a meta-analysis. Psychol Med, 40, 1797-810 https://doi.org/10.1017/S0033291709992285
  21. Prelusky D (1996). A study on the effect of deoxynivalenol on serotonin receptor binding in fig brain membranes. J Environ Sci Health B, 31, 1103-17. https://doi.org/10.1080/03601239609373056
  22. Reiche EMV, Nunes SOV, Morimoto HK (2004). Stress, depression, the immune system, and cancer. Lancet Oncol, 5, 617-25. https://doi.org/10.1016/S1470-2045(04)01597-9
  23. Shariati GR, Ahangari G, Asadi SM, Ahmadkhaniha HR (2009). Expression changes of serotonin receptor gene subtype 5ht3a in peripheral blood mononuclear cells from schizophrenic patients treated with haloperidol and olanzapin. Iran J Allergy Asthma Immunol, 8, 135-9.
  24. Siddiqui EJ, Thompson CS, Mikhailidis DP, Mumtaz FH (2005). The role of serotonin in tumour growth. Oncol Rep, 14, 1593-7.
  25. Soll C, Jang JH, Riener MO, et al. (2009). Serotonin promotes tumor growth in human hepatocellular cancer. Hepatology, 51, 1244-54.
  26. Sonier B, Arseneault M, Lavigne C, Ouellette RJ, Vaillancourt C (2006). The 5-HT2A serotoninergic receptor is expressed in the MCF-7 human breast cancer cell line and reveals a mitogenic effect of serotonin. Biochem Biophys Res Commun, 343, 1053-59. https://doi.org/10.1016/j.bbrc.2006.03.080
  27. Wang PS, Walker AM, Tsuang MT, et al (2001). Antidepressant use and the risk of breast cancer: a non-association. J Clin Epidemiol, 54, 728-34. https://doi.org/10.1016/S0895-4356(00)00354-1
  28. Webster JI, Tonelli L, Sternberg EM (2002). Neuroendocrine regulation of immunity. Annu Rev Immunol, 20, 125-63. https://doi.org/10.1146/annurev.immunol.20.082401.104914
  29. Yavuzsen T, Karadibak D, Cehreli R, Dirioz M (2012). Effect of group therapy on psychological symptoms and quality of life in Turkish patients with breast cancer. Asian Pac J Cancer Prev, 13, 5593-97. https://doi.org/10.7314/APJCP.2012.13.11.5593

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