Prostat Kanserinde Selenyumun Proteomik Temelli Bir Yaklaşımla Farklı Etkilerinin Belirlenmesi

Serum prostat spesifik antijeni (PSA) prostat kanserli hastaların tanımlanmasında kliniğe çok önemli katkı sağlamıştır. Bununla birlikte PSA’nın bazı limitasyonları bulunmaktadır. Bu durum erken tanı ve tedavide yeni biomarkerların tanımlanması ihtiyacını doğurmuştur. Klinik çalışmalara göre, selenyumun ileri ve agresif prostat kanserinde potansiyel önleyici etkisinin olduğu gösterilmiştir. Ancak bu etki mekanizmasının daha çok düşük selenyuma sahip erkeklerde etkili olduğu gösterilmiştir. Bu çalışmanın amacı, yeni tümör markerlarının araştırılması ve selenyumla indüklenen değişikliklerin proteomiks teknolojisiyle saptanmasıdır. Selenyumla muamale edilmiş BPH-1 ve LNCaP hücrelerinin bulunduğu besiyerindeki proteinler iki boyutlu elektroforez yapılmış ve MALDI-TOF-MS ile tanımlanmıştır. MALDI-TOF-MS kullanılarak ve veri tabanı araştırılması yapılarak besiyerinde eksprese olan 9 farklı protein tanımlanmıştır. Proteomikse dayalı bir yöntemle yeni tümör markerlarının araştırılması için uygun ve etkin bir yol olarak prostat kanseri ve benign prostatik hipertrofi hücrelerinin ayırımında 9 aday protein bir kemopreventif ajan olan selenyum kullanımına yanıt vermesine bağlı olarak tanımlanmıştır.

Anahtar Kelimeler:

Prostat kanseri, proteomik, selenyum

Prostat Kanserinde Selenyumun Proteomik Temelli Bir Yaklaşımla Farklı Etkilerinin Belirlenmesi

Although the induction of serum prostate specific antigen (PSA) measurements in clinical practice has been considered revolutionary in the treatment of prostate cancer in patients, accepted constraints still remain in the usage of PSA. Hence, it is crucial to identify other prostate cancer biomarkers that could contribute to early detection and prognosis. According to the clinical trials, selenium shows its potential inhibitory effects in advanced-stage or aggressive prostate cancer. But this chemopreventive effect shows inhibitory action only in men with low selenium levels. The aim of this study was to search new tumor markers and selenium induced changes utilizing proteomics technology. After profiling of the proteins found in conditioned medium (CM) of selenium treated BPH-1 and LNCaP cells via two-dimensional electrophoresis, identification was performed by matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF-MS). Nine differentially expressed proteins were identified in the CM of BPH-1 and LNCaP cells using MALDI-TOF-MS and database search. Conclusion: We procured possible and efficient way to search new tumor marker candidates by a proteomics-based analysis and identifed 9 potential candidate proteins in CM of selenium treated BPH-1 and LNCaP cells to differentiate prostate cancer response from benign prostatic hypertrophy response.

Keywords:

Prostate cancer, proteomics, selenium,

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[1]. Hartwell L, Mankoff D, Paulovich A, Ramsey S, Swisher E. Cancer biomarkers: a systems approach. Nat Biotechnol 2006; 24: 905-908. [2]. Ludwig JA, Weinstein JN. Biomarkers in cancer staging. Nat Rev Cancer 2005; 5 (11): 845-856. [3]. Chen P, Wang L, Li N, Liu Q, Ni J. Comparative proteomics analysis of sodium selenite-induced apoptosis in human prostate cancer cells. Metallomics 2013; 5(5): 541-550. [4]. Nicastro HL, Dunn BK. Selenium and prostate cancer prevention: insights from the selenium and vitamin E cancer prevention trial (SELECT). Nutrients 2013; 5(4): 1122-1148. [5]. Shibata MA, Ward JM, Devor DE, Liu ML, Green JE. Progression of prostatic intraepithelial neoplasia to invasive carcinoma in C3 (1)/SV40 large T antigen transgenic mice: histopathological and molecular biological alterations. Cancer Res 1996; 56: 4894-4903. [6]. Hurst R, Hooper L, Norat T, Lau R, Aune D, Greenwood DC, Vieira R, Collings R, Harvey LJ, Sterne JA, Beynon R, Savović J, Fairweather-Tait SJ. Selenium and prostate cancer: systematic review and meta-analysis. Am J Clin Nutr 2012; 96(1):111–22. [7]. Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, Minasian LM, Ford LG, Parnes HL, Gaziano JM, Karp DD, Lieber MM, Walther PJ, Klotz L, Parsons JK, Chin JL, Darke AK, Lippman SM, Goodman GE, Meyskens FL Jr, Baker LH. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011; 306(14): 1549-1556. [8]. Chan JM, Oh WK, Xie W, Regan MM, Stampfer MJ, King IB, Abe M, Kantoff PW. Plasma Selenium, Manganese Superoxide Dismutase, and Intermediate- or High-Risk Prostate Cancer. J Clin Oncol 2009; 27(22): 3577-3583. [9]. Boccon-Gibod L. Rising PSA with a negative biopsy. Eur Urol 2001;40 Suppl 2: 3-8. [10]. Nigro P, Pompilio G, Capogrossi MC. A key player for human disease. Cell Death Dis 2013; 4: 888. [11]. Yang H, Chen J, Yang J, Qiao S, Zhao S, Yu L. Cyclophilin A is upregulated in small cell lung cancer and activates ERK1/2 signal. Biochem Biophys Res Commun 2007; 361: 763-767. [12]. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer 2011; 11(2): 85-95. [13]. Cappello F, David S, Rappa F, Bucchieri F, Marasà L, Bartolotta TE, Farina F, Zummo G. The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase. BMC Cancer 2005; 5:139. [14]. Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 2005, 10(2): 86-103. [15]. Zamanian M, Veerakumarasivam A, Abdullah S, Rosli R. Calreticulin and cancer. Pathol Oncol Res 2013; 19: 149-154. [16]. Nagle RB. Intermediate filament expression in prostate cancer. Cancer Metast Rev 1996; 15(4): 473-482. [17]. Peehl DM. Cellular biology of prostatic growth factors. Prostate Suppl 1996; 6:74-78). [18]. Kandaş NO, Randolph C, Bosland MC. Differential Effects of Selenium on Benign and Malignant Prostate Epithelial Cells: Stimulation of LNCaP Cell Growth by Noncytotoxic, Low Selenite Concentrations. Nutr Cancer 2009; 61(2):251-264. [19]. Arner ES & Holmgren A. The thioredoxin system in cancer. Semin Cancer Biol 2006; 16(6): 420-426. [20]. Gallegos A, Berggren M, Gasdaska JR, Powis G. Mechanisms of the regulation of thioredoxin reductase activity in cancer cells by the chemopreventive agent selenium. Cancer Res 1997, 57(21): 4965-4970. [21]. Zhong W, Oberley TD. Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line. Cancer Res 2001; 61(19): 7071-7078. [22]. Lindner DJ, Hofmann ER, Karra S, Kalvakolanu DV. The interferon-beta and tamoxifen combination induces apoptosis using thioredoxin reductase. Biochim Biophys Acta 2000, 1496(2-3): 196-206. [23]. Nilsonne G, Sun X, Nyström C, Rundlöf AK, Potamitou Fernandes A, Björnstedt M, Dobra K. Selenite induces apoptosis in sarcomatoid malignant mesothelioma cells through oxidative stress. Free Radic Biol Med 2006; 41(6): 874-885. [24]. Montgomerie JZ, Gracy RW, Holshuh HJ, Keyser AJ, Bennett CJ, Schick DG. The 28K protein in urinary bladder, squamous metaplasia and urine is triosephosphate isomerase. Clin Biochem 1997; 30(8): 613-618. [25]. Chen G, Gharib TG, Huang CC, Thomas DG, Shedden KA, Taylor JM, Kardia SL, Misek DE, Giordano TJ, Iannettoni MD, Orringer MB, Hanash SM, Beer DG. Proteomic analysis of lung adenocarcinoma: identification of a highly expressed set of proteins in tumors. Clin Cancer Res 2002; 8(7): 2298-2305. [26]. Chen WZ, Pang B, Yang B, Zhou JG, Sun YH. Differential proteome analysis of conditioned medium of BPH-1 and LNCaP cells. Chin Med J (Engl) 2011; 124(22): 3806-3809.