AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression

详细信息    查看全文

• 作者：Yuantong Tian (1) (3)
  Lijing Zhao (1)
  Haitao Zhang (2)
  Xichun Liu (2)
  Lijuan Zhao (1)
  Xuejian Zhao (1)
  Yi Li (1)
  Jing Li (1)
  
• 关键词：AKR1C3 ; Prostate cancer ; Gleason score ; PSA ; Biomarker
• 刊名：Diagnostic Pathology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：9
• 期：1
• 全文大小：458 KB
• 参考文献：1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. / CA Cancer J Clin 2011,61(2):69-0. CrossRef
  2. Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr FA, Blumenstein BA, Davis MA, Goodman PJ: A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. / N Engl J Med 1989,321(7):419-24. CrossRef
  3. Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG, Loehrer PJ, Wilding G, Sears K, Culkin DJ, Thompson IM Jr, Bueschen AJ, Lowe BA: Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. / N Engl J Med 1998,339(15):1036-042. CrossRef
  4. Hellerstedt BA, Pienta KJ: The current state of hormonal therapy for prostate cancer. / CA Cancer J Clin 2002,52(3):154-79. CrossRef
  5. Knudsen KE, Penning TM: Partners in crime: deregulation of AR activity and androgen synthesis in prostate cancer. / Trends Endocrinol Metab 2010,21(5):315-24. CrossRef
  6. Lapouge G, Marcias G, Erdmann E, Kessler P, Cruchant M, Serra S, Bergerat JP, Ceraline J: Specific properties of a C-terminal truncated androgen receptor detected in hormone refractory prostate cancer. / Adv Exp Med Biol 2008, 617:529-34. CrossRef
  7. Reddy GP, Barrack ER, Dou QP, Menon M, Pelley R, Sarkar FH, Sheng S: Regulatory processes affecting androgen receptor expression, stability, and function: potential targets to treat hormone-refractory prostate cancer. / J Cell Biochem 2006,98(6):1408-423. CrossRef
  8. Hofland J, van Weerden WM, Dits NF, Steenbergen J, van Leenders GJ, Jenster G, Schroder FH, de Jong FH: Evidence of limited contributions for intratumoral steroidogenesis in prostate cancer. / Cancer Res 2010,70(3):1256-264. CrossRef
  9. Pfeiffer MJ, Smit FP, Sedelaar JP, Schalken JA: Steroidogenic enzymes and stem cell markers are upregulated during androgen deprivation in prostate cancer. / Mol Med 2011,17(7-):657-64.
  10. Byrns MC, Mindnich R, Duan L, Penning TM: Overexpression of aldo-keto reductase 1C3 (AKR1C3) in LNCaP cells diverts androgen metabolism towards testosterone resulting in resistance to the 5alpha-reductase inhibitor finasteride. / J Steroid Biochem Mol Biol 2012,130(1-):7-5. CrossRef
  11. Dozmorov MG, Azzarello JT, Wren JD, Fung KM, Yang Q, Davis JS, Hurst RE, Culkin DJ, Penning TM, Lin HK: Elevated AKR1C3 expression promotes prostate cancer cell survival and prostate cell-mediated endothelial cell tube formation: implications for prostate cancer progression. / BMC Cancer 2010, 10:672. CrossRef
  12. Fung KM, Samara EN, Wong C, Metwalli A, Krlin R, Bane B, Liu CZ, Yang JT, Pitha JV, Culkin DJ, Kropp BP, Penning TM, Lin HK: Increased expression of type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma. / Endocr Relat Cancer 2006,13(1):169-80. CrossRef
  13. Nakamura Y, Suzuki T, Nakabayashi M, Endoh M, Sakamoto K, Mikami Y, Moriya T, Ito A, Takahashi S, Yamada S, Yamada S, Arai Y, Sasano H: In situ androgen producing enzymes in human prostate cancer. / Endocr Relat Cancer 2005,12(1):101-07. CrossRef
  14. Howrey BT, Kuo YF, Lin YL, Goodwin JS: The impact of PSA screening on prostate cancer mortality and overdiagnosis of prostate cancer in the United States. / J Gerontol A Biol Sci Med Sci 2013,68(1):56-1. CrossRef
  15. Lopez-Otin C, Diamandis EP: Breast and prostate cancer: an analysis of common epidemiological, genetic, and biochemical features. / Endocr Rev 1998,19(4):365-96.
  16. Azzarello J, Fung KM, Lin HK: Tissue distribution of human AKR1C3 and rat homolog in the adult genitourinary system. / J Histochem Cytochem 2008,56(9):853-61. CrossRef
  17. Wako K, Kawasaki T, Yamana K, Suzuki K, Jiang S, Umezu H, Nishiyama T, Takahashi K, Hamakubo T, Kodama T, Naito M: Expression of androgen receptor through androgen-converting enzymes is associated with biological aggressiveness in prostate cancer. / J Clin Pathol 2008,61(4):448-54. CrossRef
  18. Arnold JT, Isaacs JT: Mechanisms involved in the progression of androgen-independent prostate cancers: it is not only the cancer cell’s fault. / Endocr Relat Cancer 2002,9(1):61-3. CrossRef
  19. Chang KH, Li R, Papari-Zareei M, Watumull L, Zhao YD, Auchus RJ, Sharifi N: Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer. / Proc Natl Acad Sci U S A 2011,108(33):13728-3733. CrossRef
  20. Wang S, Yang Q, Fung KM, Lin HK: AKR1C2 and AKR1C3 mediated prostaglandin D2 metabolism augments the PI3K/Akt proliferative signaling pathway in human prostate cancer cells. / Mol Cell Endocrinol 2008,289(1-):60-6. CrossRef
  21. Nam RK, Sugar L, Yang W, Srivastava S, Klotz LH, Yang LY, Stanimirovic A, Encioiu E, Neill M, Loblaw DA, Trachtenberg J, Narod SA, Seth A: Expression of the TMPRSS2: ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer. / Br J Cancer 2007,97(12):1690-695. CrossRef
  22. Bussemakers MJ, van Bokhoven A, Verhaegh GW, Smit FP, Karthaus HF, Schalken JA, Debruyne FM, Ru N, Isaacs WB: DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. / Cancer Res 1999,59(23):5975-979.
  23. Dabir PD, Ottosen P, Hoyer S, Hamilton-Dutoit S: Comparative analysis of three- and two-antibody cocktails to AMACR and basal cell markers for the immunohistochemical diagnosis of prostate carcinoma. / Diagn Pathol 2012, 7:81. CrossRef
  24. Yin M, Dhir R, Parwani AV: Diagnostic utility of p501s (prostein) in comparison to prostate specific antigen (PSA) for the detection of metastatic prostatic adenocarcinoma. / Diagn Pathol 2007, 2:41. CrossRef
  25. McGuire BB, Helfand BT, Loeb S, Hu Q, O’Brien D, Cooper P, Yang X, Catalona WJ: Outcomes in patients with Gleason score 8-0 prostate cancer: relation to preoperative PSA level. / BJU Int 2012,109(12):1764-769. CrossRef
  26. Ross RW, Xie W, Regan MM, Pomerantz M, Nakabayashi M, Daskivich TJ, Sartor O, Taplin ME, Kantoff PW, Oh WK: Efficacy of androgen deprivation therapy (ADT) in patients with advanced prostate cancer: association between Gleason score, prostate-specific antigen level, and prior ADT exposure with duration of ADT effect. / Cancer 2008,112(6):1247-253. CrossRef
  27. Keto CJ, Aronson WJ, Terris MK, Presti JC, Kane CJ, Amling CL, Freedland SJ: Detectable prostate-specific antigen nadir during androgen-deprivation therapy predicts adverse prostate cancer-specific outcomes: results from the SEARCH database. / Eur Urol 2012,65(3):620-27. CrossRef
  28. Mulholland DJ: PSA-negative/low prostate cancer cells: the true villains of CRPC? / Asian J Androl 2012,14(5):663-64. CrossRef
  
• 作者单位：Yuantong Tian (1) (3)
  Lijing Zhao (1)
  Haitao Zhang (2)
  Xichun Liu (2)
  Lijuan Zhao (1)
  Xuejian Zhao (1)
  Yi Li (1)
  Jing Li (1)
  
  1. College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin, China
  3. Gannan Medical University, Ganzhou, 341000, Jiangxi, China
  2. Tulane Cancer Center, Tulane University School of Medicine, 1430 Tulane Avenue SL-79, 70112, New Orleans, LA, USA
  
• ISSN：1746-1596

文摘

Background Aldo-keto reductase family 1 member C3 (AKR1C3) is a key steroidogenic enzyme that is overexpressed in prostate cancer (PCa) and is associated with the development of castration-resistant prostate cancer (CRPC). The aim of this study was to investigate the correlation between the expression level of AKR1C3 and the progression of PCa. Methods Sixty human prostate needle biopsy tissue specimens and ten LNCaP xenografts from intact or castrated male mice were included in the study. The relationship between the level of AKR1C3 expression by immunohistochemistry and evaluation factors for PCa progression, including prostate-specific antigen (PSA), Gleason score (GS) and age, were analyzed. Results Low immunoreactivity of AKR1C3 was detected in normal prostate epithelium, benign prostatic hyperplasia (BPH) and prostatic intraepithelial neoplasia (PIN). Positive staining was gradually increased with an elevated GS in PCa epithelium and LNCaP xenografts in mice after castration. The Spearman’s r values (r s) of AKR1C3 to GS and PSA levels were 0.396 (P--.025) and -0.377 (P--.036), respectively, in PCa biopsies. The r s of AKR1C3 to age was 0.76 (P--.011). No statistically significant difference was found with other variables. Conclusion Our study suggests that the level of AKR. 1C3 expression is positively correlated with an elevated GS, indicating that AKR1C3 can serve as a promising biomarker for the progression of PCa. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7748245591110149.