Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly
Yıl: 2021 Cilt: 25 Sayı: 1 Sayfa Aralığı: 46 - 53 Metin Dili: İngilizce DOI: 10.25179/tjem.2020-77471 İndeks Tarihi: 20-12-2021
Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly
Öz: Objevtive: Acromegaly is a rare disease characterized by growth hormone hypersecretion generally arising from pituitary adenomas. Survivin, an apoptosis inhibitor protein, plays an important role in cell cycle regulation and possibly involves hypophysis gland proliferation mechanisms. However, the underlying causes of somatotroph adenomas with different behaviors and useful prognostic markers are still not fully understood. We investigated possible associations between survivin gene promoter -31 GC genotypes and serum survivin level and clinical prognostic factors in acromegaly. Material and Methods: Sixty-eight acromegaly patients and 171 age-sex matched control subjects were enrolled in the study. Survivin -31 GC polymorphism was performed by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Blood GH and IGF1 levels were assayed using a chemiluminescence immunometric assay. Serum survivin levels were determined by ELISA. Results: Acromegaly patients had significantly higher serum survivin levels than controls (p=0.001). We found no significant association between acromegaly patients and controls in terms of survivin gene promoter -31 GC genotype distribution and allele frequencies. No correlation was found between disease characteristics and survivin gene polymorphisms. Conclusion: Our study suggests that serum survivin levels might be associated with acromegaly, but survivin -31 GC polymorphisms do not modify individual susceptibility to acromegaly in the Turkish population.
Anahtar Kelime: Akromegalide Survivin Promoterinin -31 G/C Polimorfizmi ve Survivin Düzeylerinin Araştırılması
Öz: Amaç: Akromegali, genellikle hipofiz adenomlarından kaynaklanan büyüme hormonu hipersekresyonu ile karakterize nadir görülen bir hastalıktır. Apoptozun bir inhibitör proteini olan survivin, hücre döngüsü düzenlemesinde önemli bir rol oynar ve hipofiz bezi proliferasyon mekanizmalarında yer alabilir. Farklı davranışlara sahip somatotrof adenomlarının gelişme mekanizmaları tam olarak anlaşılamamış ve kullanışlı prognostik faktörler saptanamamıştır. Bu çalışmada amacımız, survivin gen promotörü -31 GC genotipleri ve ayrıca serum survivin düzeyi ile akromegalide klinik prognostik faktörler arasındaki olası ilişkiyi araştırmaktı. Gereç ve Yöntemler: Çalışmaya 68 akromegali hastası ve 171 yaş-cinsiyet uyumlu kontrol hastası dâhil edildi. Survivin -31 GC polimorfizmi, bir polimeraz zincir reaksiyonu sınırlama fragmanı uzunluk polimorfizmi [polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)] kullanılarak gerçekleştirildi. Kan GH ve IGF1 seviyeleri, bir kemiluminesans immünometrik test kullanılarak analiz edildi. Serum survivin düzeyleri ELISA ile belirlenmiştir. Bulgular: Akromegali hastalarında serum survivin düzeyleri kontrol grubuna göre anlamlı derecede yüksekti (p=0,001). Akromegali hastaları ile survivin gen promotörü -31 GC genotipi ve allel frekanslarının dağılımı için kontroller arasında anlamlı bir ilişki bulunamadı. Hastalık özellikleri ile survivin gen polimorfizmleri arasında korelasyon bulunmadı. Sonuç: Çalışmamız, serum survivin düzeylerinin akromegali ile ilişkili olabileceğini, ancak survivin -31 GC polimorfizmlerinin Türklerden oluşan bir popülasyonda akromegali açısından bireysel duyarlılığı değiştirmediğini göstermiştir.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Lavrentaki A, Paluzzi A, Wass JA, Karavitaki N. Epidemiology of acromegaly: review of population studies. Pituitary. 2017;20:4-9.[Crossref] [PubMed] [PMC]
- 2. Alexander JM, Biller BM, Bikkal H, Zervas NT, Arnold A, Klibanski A. Clinically nonfunctioning pituitary tumors are monoclonal in origin. J Clin Invest. 1990;86:336-340.[Crossref] [PubMed] [PMC]
- 3. Clayton RN, Farrell WE. Pituitary tumour clonality revisited. Front Horm Res. 2004;32:186-204.[Crossref] [PubMed]
- 4. Klibanski A. Further evidence for a somatic mutation theory in the pathogenesis of human pituitary tumors. J Clin Endocrinol Metab. 1990;71:1415A- 1415C. [Crossref] [PubMed]
- 5. Lania A, Spada A. G-protein and signalling in pituitary tumours. Horm Res. 2009;71:95-100.[Crossref] [PubMed]
- 6. Montefusco L, Filopanti M, Ronchi CL, Olgiati L, La- Porta C, Losa M, Epaminonda P, Coletti F, Beck-Peccoz P, Spada A, Lania AG, Arosio M. d3-Growth hormone receptor polymorphism in acromegaly: effects on metabolic phenotype. Clin Endocrinol (Oxf). 2010;72:661-667.[Crossref] [PubMed]
- 7. Turgut S, Akın F, Ayada C, Topsakal S, Yerlikaya E, Turgut G. The growth hormone receptor polymorphism in patients with acromegaly: relationship to BMI and glucose metabolism. Pituitary. 2012;15:374-379.[Crossref] [PubMed]
- 8. Ferraù F, Romeo PD, Puglisi S, Ragonese M, Torre ML, Scaroni C, Occhi G, De Menis E, Arnaldi G, Trimarchi F, Cannavò S. Analysis of GPR101 and AIP genes mutations in acromegaly: a multicentric study. Endocrine. 2016;54:762-767.[Crossref] [PubMed]
- 9. Pepe S, Korbonits M, Iacovazzo D. Germline and mosaic mutations causing pituitary tumours: genetic and molecular aspects. J Endocrinol. 2019;240:R21-R45.[Crossref] [PubMed]
- 10. Altieri DC. Survivin, cancer networks and pathwaydirected drug discovery. Nat Rev Cancer. 2008;8:61-70.[Crossref] [PubMed]
- 11.Reed JC. The Survivin saga goes in vivo. J Clin Invest. 2001;108:965-969.[Crossref] [PubMed] [PMC]
- 12. Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, Altieri DC. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature. 1998;396:580-584.[Crossref] [PubMed]
- 13.Chen WC, Liu Q, Fu JX, Kang SY. Expression of survivin and its significance in colorectal cancer. World J Gastroenterol. 2004;10:2886-2889.[Crossref] [PubMed] [PMC]
- 14.Fields AC, Cotsonis G, Sexton D, Santoianni R, Cohen C. Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome. Mod Pathol. 2004;17:1378-1385.[Crossref] [PubMed]
- 15. Liu BB, Wang WH. Survivin and pancreatic cancer. World J Clin Oncol. 2011;2:164-168.[Crossref] [PubMed] [PMC]
- 16.Jankowska A, Wasko R, Waligorska-Stachura J, Andrusiewicz M, Jaskula M, Liebert W, Sowinski J. Survivin products in pituitary tumors. Neuro Endocrinol Lett. 2008;29:1033-1037.[PubMed]
- 17.Ademoglu E, Dilekci E, Candan Z, Gorar S, Niyazoglu M, Carlioglu A, Yildiz F, Baydar I, Aslan A. Is circulating survivin altered in acromegaly? Medicine Science. 2018;7:265-268.[Crossref]
- 18.Ben-Shlomo A, Melmed S. Acromegaly. Endocrinol Metab Clin North Am. 2008;37:101-122, viii. [Crossref] [PubMed] [PMC]
- 19. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.[Crossref] [PubMed] [PMC]
- 20. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997;3:917-921.[Crossref] [PubMed]
- 21. Ambrosini G, Adida C, Sirugo G, Altieri DC. Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting. J Biol Chem. 1998;273:11177-11182.[Crossref] [PubMed]
- 22.Bayram S, Akkız H, Bekar A, Akgöllü E. The association between the survivin -31G/C promoter polymorphism and hepatocellular carcinoma risk in a Turkish population. Cancer Epidemiol. 2011;35:555-559.[Crossref] [PubMed]
- 23. Liu Y, Li L, Qi H, Gao Y, Liu S, Xu C. Survivin -31G>C polymorphism and gastrointestinal tract cancer risk: a meta-analysis. PLoS One. 2013;8:e54081.[Crossref] [PubMed] [PMC]
- 24.Qin Q, Zhang C, Zhu H, Yang X, Xu L, Liu J, Lu J, Zhan L, Cheng H, Sun X. Association between survivin -31G>C polymorphism and cancer risk: metaanalysis of 29 studies. J Cancer Res Clin Oncol. 2014;140:179-188.[Crossref] [PubMed]
- 25.Cheng ZJ, Hu LH, Huang SJ. Correlation of -31G/C polymorphisms of survivin promoter to tumorigenesis of gastric carcinoma. Ai Zheng. 2008;27:258- 263.[PubMed]
- 26.Jang JS, Kim KM, Kang KH, Choi JE, Lee WK, Kim CH, Kang YM, Kam S, Kim IS, Jun JE, Jung TH, Park JY. Polymorphisms in the survivin gene and the risk of lung cancer. Lung Cancer. 2008;60:31-39.[Crossref] [PubMed]
- 27.Gazouli M, Tzanakis N, Rallis G, Theodoropoulos G, Papaconstantinou I, Kostakis A, Anagnou NP, Nikiteas N. Survivin -31G/C promoter polymorphism and sporadic colorectal cancer. Int J Colorectal Dis. 2009;24:145-150.[Crossref] [PubMed]
- 28.Yang L, Zhu H, Zhou B, Gu H, Yan H, Tang N, Dong H, Sun Q, Cong R, Chen G, Wang B. The association between the survivin C-31G polymorphism and gastric cancer risk in a Chinese population. Dig Dis Sci. 2009;54:1021-1028.[Crossref] [PubMed]
- 29.Herman V, Drazin NZ, Gonsky R, Melmed S. Molecular screening of pituitary adenomas for gene mutations and rearrangements. J Clin Endocrinol Metab. 1993;77:50-55.[Crossref] [PubMed]
- 30. Prezant TR, Levine J, Melmed S. Molecular characterization of the men1 tumor suppressor gene in sporadic pituitary tumors. J Clin Endocrinol Metab. 1998;83:1388-1391.[Crossref] [PubMed]
- 31.Spada A, Lania A, Ballarè E. G protein abnormalities in pituitary adenomas. Mol Cell Endocrinol. 1998;142:1-14.[Crossref] [PubMed]
- 32.Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD, Melmed S. Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab. 1999;84:761-767.[Crossref] [PubMed]
- 33. Karga HJ, Alexander JM, Hedley-Whyte ET, Klibanski A, Jameson JL. Ras mutations in human pituitary tumors. J Clin Endocrinol Metab. 1992;74:914-919. [PubMed]
- 34.Wasko R, Waligorska-Stachura J, Jankowska A, Warchol JB, Liebert W, Sowinski J. Coexpression of survivin and PCNA in pituitary tumors and normal pituitary. Neuro Endocrinol Lett. 2009;30:477- 481.[PubMed]
- 35.Liu JL, Zhang XJ, Zhang Z, Zhang AH, Wang W, Dong JH. Meta-analysis: prognostic value of survivin in patients with hepatocellular carcinoma. PLoS One. 2013;8:e83350.[Crossref] [PubMed] [PMC]
- 36.Zhang J, Zhu Z, Sun Z, Sun X, Wang Z, Xu H. Survivin gene expression increases gastric cancer cell lymphatic metastasis by upregulating vascular endothelial growth factor-C expression levels. Mol Med Rep. 2014;9:600-606.[Crossref] [PubMed]
| APA | İLHAN M, SÜRMEN S, Turgut S, KORKMAZ G, Özkan Küçük N, Karaman O, Yaylim I, Tasan E (2021). Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly. , 46 - 53. 10.25179/tjem.2020-77471 |
| Chicago | İLHAN Muzaffer,SÜRMEN Saime,Turgut Seda,KORKMAZ Gurbet,Özkan Küçük Nazlı Ezgi,Karaman Ozcan,Yaylim Ilhan,Tasan Ertugrul Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly. (2021): 46 - 53. 10.25179/tjem.2020-77471 |
| MLA | İLHAN Muzaffer,SÜRMEN Saime,Turgut Seda,KORKMAZ Gurbet,Özkan Küçük Nazlı Ezgi,Karaman Ozcan,Yaylim Ilhan,Tasan Ertugrul Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly. , 2021, ss.46 - 53. 10.25179/tjem.2020-77471 |
| AMA | İLHAN M,SÜRMEN S,Turgut S,KORKMAZ G,Özkan Küçük N,Karaman O,Yaylim I,Tasan E Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly. . 2021; 46 - 53. 10.25179/tjem.2020-77471 |
| Vancouver | İLHAN M,SÜRMEN S,Turgut S,KORKMAZ G,Özkan Küçük N,Karaman O,Yaylim I,Tasan E Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly. . 2021; 46 - 53. 10.25179/tjem.2020-77471 |
| IEEE | İLHAN M,SÜRMEN S,Turgut S,KORKMAZ G,Özkan Küçük N,Karaman O,Yaylim I,Tasan E "Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly." , ss.46 - 53, 2021. 10.25179/tjem.2020-77471 |
| ISNAD | İLHAN, Muzaffer vd. "Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly". (2021), 46-53. https://doi.org/10.25179/tjem.2020-77471 |
| APA | İLHAN M, SÜRMEN S, Turgut S, KORKMAZ G, Özkan Küçük N, Karaman O, Yaylim I, Tasan E (2021). Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly. Turkish Journal of Endocrinology and Metabolism, 25(1), 46 - 53. 10.25179/tjem.2020-77471 |
| Chicago | İLHAN Muzaffer,SÜRMEN Saime,Turgut Seda,KORKMAZ Gurbet,Özkan Küçük Nazlı Ezgi,Karaman Ozcan,Yaylim Ilhan,Tasan Ertugrul Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly. Turkish Journal of Endocrinology and Metabolism 25, no.1 (2021): 46 - 53. 10.25179/tjem.2020-77471 |
| MLA | İLHAN Muzaffer,SÜRMEN Saime,Turgut Seda,KORKMAZ Gurbet,Özkan Küçük Nazlı Ezgi,Karaman Ozcan,Yaylim Ilhan,Tasan Ertugrul Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly. Turkish Journal of Endocrinology and Metabolism, vol.25, no.1, 2021, ss.46 - 53. 10.25179/tjem.2020-77471 |
| AMA | İLHAN M,SÜRMEN S,Turgut S,KORKMAZ G,Özkan Küçük N,Karaman O,Yaylim I,Tasan E Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly. Turkish Journal of Endocrinology and Metabolism. 2021; 25(1): 46 - 53. 10.25179/tjem.2020-77471 |
| Vancouver | İLHAN M,SÜRMEN S,Turgut S,KORKMAZ G,Özkan Küçük N,Karaman O,Yaylim I,Tasan E Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly. Turkish Journal of Endocrinology and Metabolism. 2021; 25(1): 46 - 53. 10.25179/tjem.2020-77471 |
| IEEE | İLHAN M,SÜRMEN S,Turgut S,KORKMAZ G,Özkan Küçük N,Karaman O,Yaylim I,Tasan E "Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly." Turkish Journal of Endocrinology and Metabolism, 25, ss.46 - 53, 2021. 10.25179/tjem.2020-77471 |
| ISNAD | İLHAN, Muzaffer vd. "Investigation of Survivin Promoter -31 G/C Polymorphism and Survivin Levels in Acromegaly". Turkish Journal of Endocrinology and Metabolism 25/1 (2021), 46-53. https://doi.org/10.25179/tjem.2020-77471 |
