Küçük Hücreli Dışı Akciğer Kanserinde PTGS2, CALR, MAGE-A3 Genlerinin Transkripsiyon Düzeyinde İfade Analizi

Amaç: Akciğer kanserinde dolaylı yoldan karsinogenezi tetikleyen genlerdeki ifade değişimleri dikkat çekici bir konudur. Mutasyonların yanı sıra hücredeki bölünme, apoptoz, invazyon ve hücre göçleri üzerinde etkili olan genlerin ifade artışının saptanması, yeni inhibitör veya monoklonal antikor ilaçları geliştirme çalışmaları için önem arz etmektedir. Bu çalışmanın amacı, akciğer adenokarsinomunu modelleyen A549 hücre dizisinde PTGS2, CALR ve MAGE-A3 genlerinin, sağlıklı bronş epitelini modelleyen BEAS-2B hücre dizisine kıyasla ilgili genlerin ifade düzeylerini araştırılmasıdır.Materyal ve Metod: mRNA ifade seviye değişikliğini belirlemek için kantitatif Gerçek zamanlı PCR yapılmıştır.Bulgular: Çalışmanın sonucunda, A549 hücre dizisinde mRNA ekspresyon seviye farkı, BEAS-2B hücre dizisi ile karşılaştırıldığında PTGS2 geninde 229,13 kat artış; CALR geninde 4,03 kat artış; MAGE-A3 geninde 3,41 kat artış gözlendi. Bu üç genin kanser hücresi bölünmesinde, apoptoz direncinde, invazyon ve anjiyogenezde rol oynadığı bilinmektedir.Sonuç: Bu çalışmanın bir sonucu olarak, bu üç genin NF-κB sinyal yolu üzerinde birlikte etkisi olduğu düşünülmektedir. Bu üç genin bu noktada aydınlanması için protein seviyesinde araştırma yapmak faydalı olabilir.

Expression Analysis in the Transcription Level of PTGS2, CALR, MAGE-A3 Genes in Non-Small Cell Lung Cancer

Background: In lung cancer, expression changes in genes that indirectly trigger carcinogenesis are a remarkable issue. In addition to mutations, detection of expression of genes that affect cell division, apoptosis, invasion and cell migration is important for studies to develop new inhibitor or monoclonal antibody drugs. Aim of this study was to investigate the mRNA expression levels of PTGS2, CALR and MAGE-A3 genes in the A549 cell line which is modeling lung adenocarcinoma compared to the BEAS-2B cell line which is modeling healthy bronchial epithelium.Materials and Methods: Quantitative Real-time PCR was performed to obtain the mRNA expression level changing.Results: In the results of the study, the mRNA level expression difference in A549 cell line compared with BEAS-2B cell line 229,13-fold increase in PTGS2 gene; 4,03-fold increase in CALR gene; 3,41-fold increase in MAGE-A3 gene were observed. These three genes are known to play roles in cancer cell division, apoptosis resistance, invasion, and angiogenesis.Conclusions: As a result of this study, these three genes are thought to have jointly effect on the NF-κB signaling pathway. It may be beneficial to investigate on protein level for these three genes to illuminate at this point.

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  • 1. Nasim F, Sabath BF, Eapen GA. Lung cancer. Medical Clinics, 2019; 103(3): 463-473. 2. Mao M, Wu Z, Chen J. MicroRNA-187-5p suppresses cancer cell progression in non-small cell lung cancer (NSCLC) through down-regulation of CYP1B1. Biochemical and biophysical research communications, 2016; 478(2): 649-655. 3. Park JY, Pillinger MH, Abramson SB. Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clinical immunology. 2006; 119(3): 229-240. 4. Gold LI, Eggleton P, Sweetwyne MT, Van Duyn, LB, Greives MR, Naylor SM, et al. Calreticulin: non-endoplasmic reticulum functions in physiology and disease. The FASEB Journal,2011; 24(3): 665-683 5. Bajor A, Tischer S, Figueiredo C, Wittmann M, Immenschuh S, Blasczyk R,et al. Modulatory role of calreticulin as chaperokine for dendritic cell‐based immunotherapy. Clinical & Experimental Immunology.2011; 220-234 6. Fucikova J, Becht E, Iribarren K, Goc J, Remark R, Damotte D, et al. Calreticulin Expression in Human Non–Small Cell Lung Cancers Correlates with Increased Accumulation of Antitumor Immune Cells and Favorable Prognosis. Cancer research. 2016,76(7):1746-1756. 7. The Human Protein Atlas. MAGE family member A3. https://www.proteinatlas.org/ENSG00000221867-MAGEA3/pathology. 8. Lu YC, Parker LL, Lu T, Zheng Z, Toomey MA, White DE, et al. Treatment of patients with metastatic cancer using a major histocompatibility complex class II-restricted T-cell receptor targeting the cancer germline antigen MAGE-A3. Journal of clinical oncology: official journal of theAmerican Society of Clinical Oncology. 2017, 35(29): 3322-3329. 9. Daniel TO, Liu H, Morrow JD, Crews BC, Marnett LJ. Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis. Cancer research. 1999; 59(18): 4574-4577. 10. Dempke W, Rie C, Grothey A, Schmoll HJ. Cyclooxygenase-2: a novel target for cancer chemotherapy?. Journal of cancer research and clinical oncology.2001; 127(7): 411-417. 11. Hida T, Yatabe Y, Achiwa H, Muramatsu H, Kozaki KI, Nakamura S, et al. Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer research. 1998; 58(17): 3761-3764. 12. Wolff H, Saukkonen K, Anttila S, Karjalainen A, Vainio H, Ristimäki A. Expression of cyclooxygenase-2 in human lung carcinoma. Cancer research. 1998; 58(22):4997-5001 13. Li Y, Ma, C, Qian M, Wen Z, Jing H, Qianet D,et al. Butein induces cell apoptosis and inhibition of cyclooxygenase‑2 expression in A549 lung cancer cells. Molecular medicine reports.2014; 9(2): 763-767. 14. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. New England Journal of Medicine, 2013; 369(25): 2379-2390 15. Lu YC, Weng WC, Lee H. Functional roles of calreticulin in cancer biology. BioMed research international, 2015. 16. Bergner A, Kellner J, Tufman A, Huber R. Endoplasmic reticulum Ca 2+-homeostasis is altered in small and non-small cell lung cancer cell lines. Journal of Experimental & Clinical Cancer Research.2009; 28:1-25. 17. Thongprasert S, Yang PC, Lee JS, Soo R, Gruselle O, Myo A, et al. The prevalence of expression of MAGE-A3 and PRAME tumor antigens in East and South East Asian non-small cell lung cancer patients. Lung Cancer.2016; 101:137-144. 18. Chen X, Wang L, Liu J, Huang L, Yang, Gao Q, Malinowski W, et al. Expression and prognostic relevance of MAGE-A3 and MAGE-C2 in non-small cell lung cancer. Oncology Letters. 2017; 1609-1618. 19. Vansteenkiste, J., Zielinski, M., Linder, A., Dahabreh, J., Gonzalez, E. E., et al. Adjuvant MAGE-A3 immunotherapy in resected non–small-cell lung cancer: phase II randomized study results. Journal of Clinical Oncology.2013; 31(19):2396-2403. 20. Raez LE, Fein S, Podack ER. Lung cancer immunotherapy. Clinical medicine & research. 2005; 3(4): 221-228 21. Clarke C, Smyth MJ. Calreticulin exposure increases cancer immunogenicity. Nature biotechnology. 2007; 25(2): 192.
Harran Üniversitesi Tıp Fakültesi Dergisi-Cover
  • ISSN: 1304-9623
  • Yayın Aralığı: Yılda 3 Sayı
  • Başlangıç: 2004
  • Yayıncı: Harran Üniversitesi Tıp Fakültesi Dekanlığı