Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Conditional PTEN-deficient Mice as a Prostate Cancer Chemoprevention Model

  • Koike, Hiroyuki (Department of Urology, Kinki University Faculty of Medicine) ;
  • Nozawa, Masahiro (Department of Urology, Kinki University Faculty of Medicine) ;
  • De Velasco, Marco A (Department of Urology, Kinki University Faculty of Medicine) ;
  • Kura, Yurie (Department of Urology, Kinki University Faculty of Medicine) ;
  • Ando, Naomi (Department of Urology, Kinki University Faculty of Medicine) ;
  • Fukushima, Emiko (Department of Urology, Kinki University Faculty of Medicine) ;
  • Yamamoto, Yutaka (Department of Urology, Kinki University Faculty of Medicine) ;
  • Hatanaka, Yuji (Department of Urology, Kinki University Faculty of Medicine) ;
  • Yoshikawa, Kazuhiro (Cell Therapy Center, Aichi Medical University) ;
  • Nishio, Kazuto (Department of Genome Biology, Kinki University Faculty of Medicine) ;
  • Uemura, Hirotsugu (Department of Urology, Kinki University Faculty of Medicine)
  • Published : 2015.03.18
Download PDF
⟨ Previous Next ⟩

Abstract

Background: We generated a mouse model of prostate cancer based on the adult-prostate-specific inactivation of phosphatase and tensin homolog (PTEN) using the Cre-loxP system. The potential of our mice as a useful animal model was examined by evaluating the chemopreventive efficacy of the anti-androgen, chlormadinone acetate (CMA). Materials and Methods: Six-week-old mice were treated subcutaneously with $50{\mu}g/g$ of CMA three times a week for 9 or 14 weeks and sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinary tract (GUT) and histologically evident prostate gland tumor development were evaluated. Proliferation and apoptosis status in the prostate were examined by immunohistochemistry. Results: CMA triggered significant shrinkage of not only the GUT but also prostate glands at 15 weeks compared to the control (p=0.017 and p=0.010, respectively), and the trend became more marked after a further five-weeks of treatment. The onset of prostate adenocarcinoma was not prevented but the proliferation of cancer cells was inhibited by CMA, which suggested the androgen axis is critical for cancer growth in these mice. Conclusions: Conditional PTEN-deficient mice are useful as a preclinical model for chemoprevention studies and serve as a valuable tool for the future screening of potential chemopreventive agents.

Keywords

References

  1. Askari F, Parizi MK, Jessri M, et al (2014a). Dietary patterns in relation to prostate cancer in Iranian men: a case-control study. Asian Pac J Cancer Prev, 15, 2159-63. https://doi.org/10.7314/APJCP.2014.15.5.2159
  2. Askari F, Parizi MK, Jessri M, et al (2014b). Fruit and vegetable intake in relation to prostate cancer in Iranian men: a casecontrol study. Asian Pac J Cancer Prev, 13, 5223-7.
  3. Daniyal M, Siddiqui ZA, Akram M, et al (2014). Epidemiology, etiology, diagnosis and treatment of prostate cancer. Asian Pac J Cancer Prev, 15, 9575-8. https://doi.org/10.7314/APJCP.2014.15.22.9575
  4. Davies MA (2011). Regulation, role, and targeting of Akt in cancer. J Clin Oncol, 29, 4715-7. https://doi.org/10.1200/JCO.2011.37.4751
  5. De Bono JS, Oudard S, Ozguroglu M, et al (2010). Prednisone plus cabazitaxel or mitoxantrone for metastatic castrationresistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet, 376, 1147-54. https://doi.org/10.1016/S0140-6736(10)61389-X
  6. De Velasco MA, Tanaka M, Yamamoto Y, et al (2014). Androgen deprivation induces phenotypic plasticity and promotes resistance to molecular targeted therapy in a PTEN-deficient mouse model of prostate cancer. Carcinogenesis, 35, 2142-53. https://doi.org/10.1093/carcin/bgu143
  7. Dong HV, Lee AH, Nga NH, et al (2014). Epidemiology and prevention of prostate cancer in Vietnam. Asian Pac J Cancer Prev, 15, 9747-51. https://doi.org/10.7314/APJCP.2014.15.22.9747
  8. Fizazi K, Scher HI, Molina A, et al (2012). Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol, 13, 983-92. https://doi.org/10.1016/S1470-2045(12)70379-0
  9. Garg M, Dalela D, Goel A, et al (2014). Prevention of prostate cancer with vitamins-current perspectives. Asian Pac J Cancer Prev, 15, 1897-904. https://doi.org/10.7314/APJCP.2014.15.5.1897
  10. Ittmann M, Huang J, Radaelli E, et al (2013). Animal models of human prostate cancer: the consensus report of the New York meeting of the mouse models of human cancers consortium prostate pathology committee. Cancer Res, 73, 2718-36. https://doi.org/10.1158/0008-5472.CAN-12-4213
  11. Kodama T, Wakisaka M, Shimazaki J (1980). Binding of chlormadinone acetate to cytosol from human benign prostatic hypertrophy. Endocrinol Jpn, 27, 53-7. https://doi.org/10.1507/endocrj1954.27.53
  12. Maehama T, Dixon JE (1998). The tumor suppressor, PTEN/ MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem, 273, 13375-8. https://doi.org/10.1074/jbc.273.22.13375
  13. McCall P, Witton CJ, Grimsley S, et al (2008). Is PTEN loss associated with clinical outcome measures in human prostate cancer? Br J Cancer, 99, 1296-301. https://doi.org/10.1038/sj.bjc.6604680
  14. McGrowder DA, Jackson LA, Crawford TV (2012). Prostate cancer and metabolic syndrome: is there a link? Asian Pac J Cancer Prev, 13, 1-13. https://doi.org/10.7314/APJCP.2012.13.1.001
  15. Parisotto M, Metzger D (2013). Genetically engineered mouse models of prostate cancer. Mol Oncol, 7, 190-205. https://doi.org/10.1016/j.molonc.2013.02.005
  16. Pienta KJ, Bradley D (2006). Mechanisms underlying the development of androgen-independent prostate cancer. Clin Cancer Res, 12, 1665-71. https://doi.org/10.1158/1078-0432.CCR-06-0067
  17. Saw CL, Wu TY, Paredes-Gonzalez X, et al (2011). Pharmacodynamics of fish oil: protective effects against prostate cancer in TRAMP mice fed with a high fat western diet. Asian Pac J Cancer Prev, 12, 3331-4.
  18. Scher HI, Fizazi K, Saad F, et al (2012). Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med, 367, 1187-97. https://doi.org/10.1056/NEJMoa1207506
  19. Shappell SB, Thomas GV, Roberts RL, et al (2004). Prostate pathology of genetically engineered mice: definitions and classification. the consensus report from the bar harbor meeting of the mouse models of human cancer consortium prostate pathology committee. Cancer Res, 64, 2270-305. https://doi.org/10.1158/0008-5472.CAN-03-0946
  20. Siegel R, Ma J, Zou Z, et al (2014). Cancer statistics, 2014. CA Cancer J Clin, 64, 9-29. https://doi.org/10.3322/caac.21208
  21. Sugiyama Y, Masumori N, Fukuta F, et al (2013). Influence of isoflavone intake and equol-producing intestinal flora on prostate cancer risk. Asian Pac J Cancer Prev, 14, 1-4. https://doi.org/10.7314/APJCP.2013.14.1.1
  22. Tewari R, Chhabra M, Natu SM, et al (2014). Significant association of metabolic indices, lipid profile, and androgen levels with prostate cancer. Asian Pac J Cancer Prev, 15, 9841-6. https://doi.org/10.7314/APJCP.2014.15.22.9841
  23. Yang L, Pascal M, Wu XH (2013). Review of selenium and prostate cancer prevention. Asian Pac J Cancer Prev, 14, 2181-4. https://doi.org/10.7314/APJCP.2013.14.4.2181
  24. Yoshimoto M, Cunha IW, Coudry RA, et al (2007). FISH analysis of 107 prostate cancers shows that PTEN genomic deletion is associated with poor clinical outcome. Br J Cancer, 97, 678-85. https://doi.org/10.1038/sj.bjc.6603924
  25. Zhou XF, Ding ZS, Liu NB (2013). Allium vegetables and risk of prostate cancer: evidence from 132,192 subjects. Asian Pac J Cancer Prev, 14, 4131-4. https://doi.org/10.7314/APJCP.2013.14.7.4131