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Pro-Enflamatuvar Sitokin IL-1β'nın İnsan Akciğer Kanseri Hücrelerinde Urotensin II Gen Ekspresyonu Üzerine Etkisi

Year 2018, Volume: 10 Issue: 3, 354 - 359, 23.10.2018
https://doi.org/10.18521/ktd.398669

Abstract

Amaç: Akciğer kanseri dünya çapında en ölümcül kanser türüdür. Akciğer kanseri hastalarının kötü prognozu ve etkili tedavinin olmaması akciğer kanseri patogenezinin ayrıntılı olarak anlaşılmasını gerektirir. Bazı çalışmalarda, U-II'nin akciğer kanseri gibi bazı hastalıkların önlenmesi ve tedavisinde olası biyobelirteç veya moleküler hedef olma durumu vurgulanmaktadır. Ancak, U-II‟nin moleküler aksiyon mekanizması henüz aydınlatılmamıştır. Bu çalışmada, akciğer kanserinde U-II'nin rolünü araştırmayı amaçladık.

Gereç ve Yöntem: Çalışmamızda A549 hücre dizileri farklı doz ve sürelerde IL-1β ile uyarıldı (1, 3 ng/ml; 6, 24 saat). GAPDH, NF-κB1, MMP-1 ve U-II mRNA seviyeleri RT-qPCR yöntemi ile analiz edildi. Verilerin analizinde delta delta CT (ΔΔCt) metodu kullanıldı. Analiz edilen veriler „katlı değişim‟ olarak ifade edildi.

Bulgular: Bulgularımız, A549 hücrelerinde U-II geninin eksprese edildiğini ve A549 hücrelerinde IL-1β'nın U-II, MMP-1 ve NF-κB1 gen ekspresyonlarını indükleyebildiğini göstermektedir.

Sonuç: U-II, akciğer kanseri tedavisinde ve önlenmesinde umut verici bir moleküler hedeftir. Bu nedenle, akciğer adenokarsinomasında U-II'nin moleküler mekanizmasını aydınlatmak için daha ileri çalışmalara ihtiyaç vardır.

References

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  • 4. Colotta F, Allavena P, Sica A, et al. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073-81.
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  • 12. Bhat IA, Naykoo NA, Qasim I, et al. Association of interleukin 1 beta (IL-1beta) polymorphism with mRNA expression and risk of non small cell lung cancer. Meta gene. 2014;2:123-33.
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  • 21. Morimoto R, Satoh F, Murakami O, et al. Immunolocalization of urotensin II and its receptor in human adrenal tumors and attached non-neoplastic adrenal tissues. Peptides. 2008;29(5):873-80.
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  • 24. Zhou CH, Wan YY, Chu XH, et al. Urotensin II contributes to the formation of lung adenocarcinoma inflammatory microenvironment through the NF-kappaB pathway in tumor-bearing nude mice. Oncology letters. 2012;4(6):1259-63.
  • 25. Balakan O, Kalender ME, Suner A, et al. The relationship between urotensin II and its receptor and the clinicopathological parameters of breast cancer. Medical science monitor : international medical journal of experimental and clinical research. 2014;20:1419-25.
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  • 27. Takahashi K, Totsune K, Murakami O, et al. Expression of urotensin II and urotensin II receptor mRNAs in various human tumor cell lines and secretion of urotensin II-like immunoreactivity by SW-13 adrenocortical carcinoma cells. Peptides. 2001;22(7):1175-9.
  • 28. Dinarello CA. Why not treat human cancer with interleukin-1 blockade? Cancer metastasis reviews. 2010;29(2):317-29.
  • 29. Johns DG, Ao Z, Naselsky D, et al. Urotensin-II-mediated cardiomyocyte hypertrophy: effect of receptor antagonism and role of inflammatory mediators. Naunyn-Schmiedeberg's archives of pharmacology. 2004;370(4):238-50.
  • 30. Segain JP, Rolli-Derkinderen M, Gervois N, et al. Urotensin II is a new chemotactic factor for UT receptor-expressing monocytes. Journal of immunology. 2007;179(2):901-9.
  • 31. Pritchard SC, Nicolson MC, Lloret C, et al. Expression of matrix metalloproteinases 1, 2, 9 and their tissue inhibitors in stage II non-small cell lung cancer: implications for MMP inhibition therapy. Oncology reports. 2001;8(2):421-4.
  • 32. Schutz A, Schneidenbach D, Aust G, et al. Differential expression and activity status of MMP-1, MMP-2 and MMP-9 in tumor and stromal cells of squamous cell carcinomas of the lung. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2002;23(3):179-84.
  • 33. Boire A, Covic L, Agarwal A, et al. PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell. 2005;120(3):303-13.
  • 34. Vincenti MP, Brinckerhoff CE. Signal transduction and cell-type specific regulation of matrix metalloproteinase gene expression: can MMPs be good for you? Journal of cellular physiology. 2007;213(2):355-64.
  • 35. Armstrong DA, Phelps LN, Vincenti MP. CCAAT enhancer binding protein-beta regulates matrix metalloproteinase-1 expression in interleukin-1beta-stimulated A549 lung carcinoma cells. Molecular cancer research : MCR. 2009;7(9):1517-24.
  • 36. Tang X, Liu D, Shishodia S, et al. Nuclear factor-kappaB (NF-kappaB) is frequently expressed in lung cancer and preneoplastic lesions. Cancer. 2006;107(11):2637-46.
  • 37. Hoesel B, Schmid JA. The complexity of NF-kappaB signaling in inflammation and cancer. Molecular cancer. 2013;12:86.

Effect of Pro-Inflammatory Cytokine IL-1β, on Urotensin II Gene Expression in Human Lung Cancer Cells

Year 2018, Volume: 10 Issue: 3, 354 - 359, 23.10.2018
https://doi.org/10.18521/ktd.398669

Abstract

Objective: Lung cancer is the deadliest cancer type world-wide. Poor prognosis of lung cancer patients and lack of an effective treatment require detailed understanding of lung cancer pathogenesis. It was highlighted in some studies that U-II is likely to be a biomarker or molecular target for the prevention and treatment of some diseases such as lung cancer. But its molecular action mechanism has not been elucidated yet. In the present study, we aimed to investigate the role of U-II in lung cancer.

Methods: In our study, A549 cells were induced with different doses of IL-1β at different durations (1, 3 ng/ml; 6, 24 hours). mRNA levels of GAPDH, NF-κB1, MMP-1, and U-II were analyzed with RT-qPCR. The Delta Delta Ct (ΔΔCt) method was used for data analysis. The analyzed data were expressed as the “fold-change”.

Results: Our results indicate that U-II gene is expressed in A549 cells and IL-1β can induce gene expressions of U-II, MMP-1 and NF-κB1 in A549 cells.

Conclusions: U-II is a promising molecular target in treatment and prevention of lung cancer. Therefore, further studies are needed to enlighten molecular mechanism of U-II in lung adenocarcinoma.

References

  • 1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International journal of cancer. 2015;136(5):E359-86.
  • 2. McIntyre A, Ganti AK. Lung cancer-A global perspective. Journal of surgical oncology. 2017;115(5):550-4.
  • 3. Atsumi T, Singh R, Sabharwal L, et al. Inflammation amplifier, a new paradigm in cancer biology. Cancer research. 2014;74(1):8-14.
  • 4. Colotta F, Allavena P, Sica A, et al. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073-81.
  • 5. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883-99.
  • 6. Hussain SP, Harris CC. Inflammation and cancer: an ancient link with novel potentials. International journal of cancer. 2007;121(11):2373-80.
  • 7. Zhang Y, Kong W, Jiang J. Prevention and treatment of cancer targeting chronic inflammation: research progress, potential agents, clinical studies and mechanisms. Science China Life sciences. 2017;60(6):601-16.
  • 8. Cho WC, Kwan CK, Yau S, et al. The role of inflammation in the pathogenesis of lung cancer. Expert opinion on therapeutic targets. 2011;15(9):1127-37.
  • 9. Engels EA. Inflammation in the development of lung cancer: epidemiological evidence. Expert review of anticancer therapy. 2008;8(4):605-15.
  • 10. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-74.
  • 11. Azad N, Rojanasakul Y, Vallyathan V. Inflammation and lung cancer: roles of reactive oxygen/nitrogen species. Journal of toxicology and environmental health Part B, Critical reviews. 2008;11(1):1-15.
  • 12. Bhat IA, Naykoo NA, Qasim I, et al. Association of interleukin 1 beta (IL-1beta) polymorphism with mRNA expression and risk of non small cell lung cancer. Meta gene. 2014;2:123-33.
  • 13. Mayne ST, Buenconsejo J, Janerich DT. Previous lung disease and risk of lung cancer among men and women nonsmokers. American journal of epidemiology. 1999;149(1):13-20.
  • 14. Bar D, Apte RN, Voronov E, et al. A continuous delivery system of IL-1 receptor antagonist reduces angiogenesis and inhibits tumor development. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2004;18(1):161-3.
  • 15. Dinarello CA. The paradox of pro-inflammatory cytokines in cancer. Cancer metastasis reviews. 2006;25(3):307-13.
  • 16. Elaraj DM, Weinreich DM, Varghese S, et al. The role of interleukin 1 in growth and metastasis of human cancer xenografts. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006;12(4):1088-96.
  • 17. Ames RS, Sarau HM, Chambers JK, et al. Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14. Nature. 1999;401(6750):282-6.
  • 18. Pearson D, Shively JE, Clark BR, et al. Urotensin II: a somatostatin-like peptide in the caudal neurosecretory system of fishes. Proceedings of the National Academy of Sciences of the United States of America. 1980;77(8):5021-4.
  • 19. Davenport AP, Maguire JJ. Urotensin II: fish neuropeptide catches orphan receptor. Trends in pharmacological sciences. 2000;21(3):80-2.
  • 20. Takahashi K, Totsune K, Murakami O, et al. Expression of urotensin II and its receptor in adrenal tumors and stimulation of proliferation of cultured tumor cells by urotensin II. Peptides. 2003;24(2):301-6.
  • 21. Morimoto R, Satoh F, Murakami O, et al. Immunolocalization of urotensin II and its receptor in human adrenal tumors and attached non-neoplastic adrenal tissues. Peptides. 2008;29(5):873-80.
  • 22. Shenouda A, Douglas SA, Ohlstein EH, et al. Localization of urotensin-II immunoreactivity in normal human kidneys and renal carcinoma. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 2002;50(7):885-9.
  • 23. Wu YQ, Song Z, Zhou CH, et al. Expression of urotensin II and its receptor in human lung adenocarcinoma A549 cells and the effect of urotensin II on lung adenocarcinoma growth in vitro and in vivo. Oncology reports. 2010;24(5):1179-84.
  • 24. Zhou CH, Wan YY, Chu XH, et al. Urotensin II contributes to the formation of lung adenocarcinoma inflammatory microenvironment through the NF-kappaB pathway in tumor-bearing nude mice. Oncology letters. 2012;4(6):1259-63.
  • 25. Balakan O, Kalender ME, Suner A, et al. The relationship between urotensin II and its receptor and the clinicopathological parameters of breast cancer. Medical science monitor : international medical journal of experimental and clinical research. 2014;20:1419-25.
  • 26. Zeng ZP, Liu GQ, Li HZ, et al. The effects of urotensin-II on proliferation of pheochromocytoma cells and mRNA expression of urotensin-II and its receptor in pheochromocytoma tissues. Annals of the New York Academy of Sciences. 2006;1073:284-9.
  • 27. Takahashi K, Totsune K, Murakami O, et al. Expression of urotensin II and urotensin II receptor mRNAs in various human tumor cell lines and secretion of urotensin II-like immunoreactivity by SW-13 adrenocortical carcinoma cells. Peptides. 2001;22(7):1175-9.
  • 28. Dinarello CA. Why not treat human cancer with interleukin-1 blockade? Cancer metastasis reviews. 2010;29(2):317-29.
  • 29. Johns DG, Ao Z, Naselsky D, et al. Urotensin-II-mediated cardiomyocyte hypertrophy: effect of receptor antagonism and role of inflammatory mediators. Naunyn-Schmiedeberg's archives of pharmacology. 2004;370(4):238-50.
  • 30. Segain JP, Rolli-Derkinderen M, Gervois N, et al. Urotensin II is a new chemotactic factor for UT receptor-expressing monocytes. Journal of immunology. 2007;179(2):901-9.
  • 31. Pritchard SC, Nicolson MC, Lloret C, et al. Expression of matrix metalloproteinases 1, 2, 9 and their tissue inhibitors in stage II non-small cell lung cancer: implications for MMP inhibition therapy. Oncology reports. 2001;8(2):421-4.
  • 32. Schutz A, Schneidenbach D, Aust G, et al. Differential expression and activity status of MMP-1, MMP-2 and MMP-9 in tumor and stromal cells of squamous cell carcinomas of the lung. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2002;23(3):179-84.
  • 33. Boire A, Covic L, Agarwal A, et al. PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell. 2005;120(3):303-13.
  • 34. Vincenti MP, Brinckerhoff CE. Signal transduction and cell-type specific regulation of matrix metalloproteinase gene expression: can MMPs be good for you? Journal of cellular physiology. 2007;213(2):355-64.
  • 35. Armstrong DA, Phelps LN, Vincenti MP. CCAAT enhancer binding protein-beta regulates matrix metalloproteinase-1 expression in interleukin-1beta-stimulated A549 lung carcinoma cells. Molecular cancer research : MCR. 2009;7(9):1517-24.
  • 36. Tang X, Liu D, Shishodia S, et al. Nuclear factor-kappaB (NF-kappaB) is frequently expressed in lung cancer and preneoplastic lesions. Cancer. 2006;107(11):2637-46.
  • 37. Hoesel B, Schmid JA. The complexity of NF-kappaB signaling in inflammation and cancer. Molecular cancer. 2013;12:86.
There are 37 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Hamza Malik Okuyan

Menderes Yusuf Terzi This is me

Cansu Önlen Güneri

Meral Urhan Küçük

Publication Date October 23, 2018
Acceptance Date July 26, 2018
Published in Issue Year 2018 Volume: 10 Issue: 3

Cite

APA Okuyan, H. M., Terzi, M. Y., Önlen Güneri, C., Urhan Küçük, M. (2018). Effect of Pro-Inflammatory Cytokine IL-1β, on Urotensin II Gene Expression in Human Lung Cancer Cells. Konuralp Medical Journal, 10(3), 354-359. https://doi.org/10.18521/ktd.398669
AMA Okuyan HM, Terzi MY, Önlen Güneri C, Urhan Küçük M. Effect of Pro-Inflammatory Cytokine IL-1β, on Urotensin II Gene Expression in Human Lung Cancer Cells. Konuralp Medical Journal. October 2018;10(3):354-359. doi:10.18521/ktd.398669
Chicago Okuyan, Hamza Malik, Menderes Yusuf Terzi, Cansu Önlen Güneri, and Meral Urhan Küçük. “Effect of Pro-Inflammatory Cytokine IL-1β, on Urotensin II Gene Expression in Human Lung Cancer Cells”. Konuralp Medical Journal 10, no. 3 (October 2018): 354-59. https://doi.org/10.18521/ktd.398669.
EndNote Okuyan HM, Terzi MY, Önlen Güneri C, Urhan Küçük M (October 1, 2018) Effect of Pro-Inflammatory Cytokine IL-1β, on Urotensin II Gene Expression in Human Lung Cancer Cells. Konuralp Medical Journal 10 3 354–359.
IEEE H. M. Okuyan, M. Y. Terzi, C. Önlen Güneri, and M. Urhan Küçük, “Effect of Pro-Inflammatory Cytokine IL-1β, on Urotensin II Gene Expression in Human Lung Cancer Cells”, Konuralp Medical Journal, vol. 10, no. 3, pp. 354–359, 2018, doi: 10.18521/ktd.398669.
ISNAD Okuyan, Hamza Malik et al. “Effect of Pro-Inflammatory Cytokine IL-1β, on Urotensin II Gene Expression in Human Lung Cancer Cells”. Konuralp Medical Journal 10/3 (October 2018), 354-359. https://doi.org/10.18521/ktd.398669.
JAMA Okuyan HM, Terzi MY, Önlen Güneri C, Urhan Küçük M. Effect of Pro-Inflammatory Cytokine IL-1β, on Urotensin II Gene Expression in Human Lung Cancer Cells. Konuralp Medical Journal. 2018;10:354–359.
MLA Okuyan, Hamza Malik et al. “Effect of Pro-Inflammatory Cytokine IL-1β, on Urotensin II Gene Expression in Human Lung Cancer Cells”. Konuralp Medical Journal, vol. 10, no. 3, 2018, pp. 354-9, doi:10.18521/ktd.398669.
Vancouver Okuyan HM, Terzi MY, Önlen Güneri C, Urhan Küçük M. Effect of Pro-Inflammatory Cytokine IL-1β, on Urotensin II Gene Expression in Human Lung Cancer Cells. Konuralp Medical Journal. 2018;10(3):354-9.