Gene Expression of P53 and Bcl-2 as Markers of Prostate Cancer Progression

Authors

  • Bungaran Sihombing Division of Urology, Faculty of Medicine, Prima University Medan, Indonesia

  • Sumaryati Syukur Department of Chemistry, Faculty of Mathematics and Natural Sciences, Andalas University, Padang, Indonesia
  • Sanusi Ibrahim Department of Chemistry, Faculty of Mathematics and Natural Sciences, Andalas University, Padang, Indonesia
  • Djong Hon Cong Department of Biology, Faculty of Mathematics and Natural Sciences, Andalas University, Padang, Indonesia
  • Didik Setyoheryanto Division of Pathology Anatomy Gajah Mada University Yogyakarta, Indonesia

Keywords:

Prostate cancer, p53, bcl-2, gene expression, gleason score.

Abstract

Introduction: Apoptotic genes regulate apoptosis by the action of their pro- and antiapoptotic products. Among the most important proteins are p53 and Bcl-2 proteins. The rate of tumor growth is dependent on the balance between proliferation and apoptosis at all stages of carcinogenesis. The differential expression of these apoptotic genes was analyzed in relation to clinicopathological criteria as Gleason Score in man with Prostate Cancer. Every prostate cancer patient who underwent histopathology examination which fulfill the criteria were included in the study. Samples then rearrange into low Gleason Score (2-6) and high Gleason Score (7-10). All samples then underwent gene expression assay for p53 and bcl-2 to be analyzed for each’s relationship with each group. The aim of this study was to evaluate tumor proliferation and the expression of the proto-oncogene Bcl-2 and tumor suppressor gene p53 in patients undergoing transurethral prostatectomy for prostate cancer, and to define their prognostic roles through correlation with final Gleason score, using qRTPCR.. A total of 40 samples consisting of 28 GS (2-6) and 12 GS (7-10) samples were included in the study. There was a significant mean difference between p53 mRNA in the GS 2-6 and 7-10 groups (p <0.001), but not for bcl-2 mRNA. Based on a multivariate analysis, only p53 mRNA had a significant association with the GS group in Adenocarcinoma Prostate with p = 0.014, 95% CI 0.926-0.991 with a predicted value of 77.5%. We conclude that p53 mRNA is an independent predictive factor of Gleason Score-based progression of adenocarcinoma Prostate.

References

[1]. B Sihombing, Jamaludin, DH Cong, S Ibrahim, S Syukur. “Immunohistohemical detection on p53 protein as a prognostic indicator in prostate carcinoma.” The Journal of Chemical and Pharmaceutical Research, vol. 7(9), pp. 10. 2015.
[2]. C Caulin, T Nguyen, GA Lang, TM Goepfert, BR Brinkley, WW Cai, G Lozano, and DR Roop. “An inducible mouse model for skin cancer reveals distinct roles for gain- and loss-of-function p53 mutations.” J Clin Invest. vol. 117(7). pp.1893-901. 2007.
[3]. G Liu, TJ McDonnell, R Montes de Oca Luna, M Kapoor, B Mims, AK El-Naggar, and G Lozano. “High metastatic potential in mice inheriting a targeted p53 missense mutation.” Proc Natl Acad Sci USA, vol. 97, pp. 4174- 9. 2000.
[4]. M Seto, U Jaeger, RD Hockett, W Graninger, S Bennett, et al. “Alternative pro- moters and exons, somatic mutation and deregulation of the bcl-2-Ig fusion gene in lymphoma.” The EMBO Journal, vol. 7, pp. 123 - 131. 1988.
[5]. TJ McDonnell, NM Navone, P Troncoso, et al. “Expression of bcl-2 oncoprotein and p53 protein accumulation in bone mar- row metastases of androgen independent prostate cancer.” J Urol., vol. 157(2), pp. 569-74. 1997.
[6]. T Visakorpi. “Proliferative activity determined by DNA flow cytometry and proliferating cell nuclear antigen (PCNA) immunohistochemistry as a prognostic factor in prostatic carcinoma.” The Journal of Pathology, vol. 168(1), pp. 7-13.1992.
[7]. F Hofstädter, R Knüchel, J Rüschoff. “Cell proliferation assessment in oncology.” Virchows Arch., vol. 427(3), pp. 323-41. 1995.
[8]. DF Gleason. “Classification of prostatic carcinomas.” Cancer Chemother Rep, vol. 50(3), pp. 125-8. 1996.
[9]. DF Gleason, GT Mellinger. “Prediction of prognosis for prostatic adeno- carcinoma by combined histological grading and clinical staging.” J Urol, vol. 111(1), pp. 58-64. 1974.
[10]. T Gevaert. Belgian Journal of Medical Oncolog,. vol. 6(2). 2012.
[11]. S Syukur, Syafrizayanti, S Zulaiha. “Virgin coconut oil increase HDL, lower triglyceride and fatty acids profile in blood Serum of mus musculus.” The Research Journal of Chemical and Pharmaceutical, vol. 8(2), pp. 1077. 2017.
[12]. HD Van Guilder, KE Vrana, WM Freeman. “Twenty-five years of quantitative PCR for gene expression analysis.” Biotechniques, vol. 44(5), pp. 619 – 626 .2008.
[13]. HL Tobing, S Syukur, E Purwati, R Zein, R Muzahar, et al. “Comparison of SD bio line malaria Ag-Pf/pan test with microscopic examination for detection of P.Falciparum, P.Vivax and Mixed infection in South Nias, North Sumatera, Indonesia.” The Research Journal of Pharmaceutical, Biological and Chemical Sciences, vol. 6 (3), pp. 917. 2015.
[14]. A Chetcuti, S Margan, S Mann, P Russell, D Handelsman, J Rogers, Q Dong. Identification of differentially expressed genes in organ-confined prostate cancer by gene expression array. Prostate, vol. 47(2), pp. 132–40. 2001.
[15]. Y Ding, L Xu, S Chen, BD Jovanovic, IB Helenowski, DL Kelly, WJ Catalona, XJ Yang, M Pins, V Ananthanarayanan, RC Bergan. “Characterization of a method for profiling gene expression in cells recovered from intact human prostate tissue using RNA linear amplification.” Prostate Cancer Prostatic Dis, vol. 9(4), pp. 379–91. 2006.
[16]. M Azhar, D Natalia, S Syukur, Vovien, and Jamasari. “Gene Fragments that encodes inulin hydrolysis enzyme from genomic Bacillus licheniformis: Isolation by PCR technique using new primers.” International Journal of Biological Chemistry, vol. 9(2), pp. 59. 2015.
[17]. Campos. “DNA Extraction from Formalin-Fixed Material.” Methods in molecular biology. January, 2012.
[18]. J Jozefczuk, H Stachelscheid, L Chavez, R Herwig, H Lehrach, K Zeilinger, JC Gerlach, and J Adjaye. “Molecular characterization of cultured adult human liver progenitor cells.” Tissue Eng. Part C Methods, vol. 16(5), pp. 821–34. 2010.
[19]. R Boland and L Riccardiello. “How many mutations does it take to make a tumor?” Proc Natl Acad Sci USA, vol. 96, pp. 14675-7. 1999.
[20]. MJ Renan. “How many mutations are required for tumorigenesis? Implications from human cancer data.” Molecular Carcinogenesis, vol. 7, pp. 139 – 146. 1993.
[21]. R Bernards and RA Weinberg. “A progression puzzle – metastasis genes.” Nature, vol. 418, pp. 823. 2002.
[22]. TM Pisansky, MJ Kahn, DG Bostwick. “An enhanced progostic system for clinically localized carcinoma of the prostate.” Cancer, vol. 79, pp. 2154-2161. 1997.
[23]. W Coleman, and G Tsongalis. “The Molecular Basis of Human Cancer (1 st).” Humana Press Inc. 2002.
[24]. F MacDonald, CHJ Ford, and AG Casson. “Molecular Biology of Cancer” in MacDonald, 2nd ed, 2004.
[25]. TJ McDonnell, P Troncoso, SM Brisbay, C Logothetis, LWK Chung, JT Hsieh, SM Tu, and ML Campbell. “Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer.” Cancer Res., vol. 52, pp. 6940-4. 1992.
[26]. GJ Berchem, M Bosseler, LY Sugars, HJ Voeller, S Zeitlin, et al. “Androgens induce resistance to bcl-2-mediated apoptosis in LNCaP prostate cancer cells.” Cancer Res, vol. 55, pp. 735-8. 1995.
[27]. P Rodriguez-Tome, T Flores, M Hollstein, CC Harris, R Montesano. “IARC Database of p53 gene mutations in human tumors and cell lines: updated compilation, revised formats and new visualisation tools.” Nucleic Acids Research, vol. 26, pp. 205 – 213. 1998.
[28]. TH Ecke, HH Schlechte, A Hübsch, SV Lenk, K Schiemenz, BD Rudolph, K Miller. “TP53Mutation in prostate needle biopsies – comparison with patients follow-up.” Anticancer Res, vol. 27(6), pp. 4143-8. 2007.
[29]. D Sidransky and M Hollstein. “Clinical implications of the p53 gene.” Annual Review of Medicine, vol. 47, pp. 285-301. 1996.
[30]. JA Blondal and S Benchimol. “The role of p53 in tumor progression.” Semin Cancer Biol, vol. 5, pp. 177-86. 1994.
[31]. MRA Mowat. “p53 in tumor progression: Life, death, and everything.” Advanced Cancer Research, vol. 74, pp. 25-48. 1998.
[32]. MA Kuczyk, J Serth, C Bokemeyer, S Machtens, A Minssen, W Bathke, J Hartmann, and U Jonas. “The prognostic value of p53 for long-term and recurrence-free survival following radical prostatectomy.” Eur J Cancer, vol. 34, pp. 679-86. 1998.

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Published

2017-08-18

How to Cite

Sihombing, B., Syukur, S., Ibrahim, S., Hon Cong, D., & Setyoheryanto, D. (2017). Gene Expression of P53 and Bcl-2 as Markers of Prostate Cancer Progression. American Scientific Research Journal for Engineering, Technology, and Sciences, 35(1), 8–14. Retrieved from https://asrjetsjournal.org/index.php/American_Scientific_Journal/article/view/3226

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