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Abnormalities of apoptotic and cell cycle regulatory proteins in distinct histopathologic components of benign prostatic hyperplasia

Abstract

Introduction:Benign prostatic hyperplasia (BPH) is a slowly progressive abnormal glandular enlargement with heterogeneous morphology. Disruption of apoptotic pathways has been suggested as an important regulatory mechanism in this common and significantly morbid disease.

Methods:Prostatic tissue from 20 patients with BPH and no prior or subsequent prostatic carcinoma was obtained by transurethral prostatectomy (TURP) at the University of California Davis. Apoptotic regulatory proteins: BCL2, BAX and p27 were analyzed by immunohistochemistry and evaluated for expression in four distinct histologic patterns: hyperplastic epithelium, nodules, dilated glands and atrophic/inflammatory glands.

Results:Particularly striking was the decreased expression of BAX and an abnormal BCL2 : BAX ratio within all nodules relative to expression in other epithelial patterns. p27 expression was decreased in 35% of the hyperplastic epithelial areas and 10% of the nodules.

Discussion:Overall, abnormal expression of BCL2, BAX and/or p27 was identified in the hyperplastic epithelium of 19 (90%) of specimens and all 12 (100%) of the hyperplastic nodules. The high frequency of abnormalities in apoptosis regulatory genes, suggests that alteration of apoptotic pathways is important for the development of this condition.

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References

  1. Kortt MA, Bootman JL . The economics of benign prostatic hyperplasia treatment: a literature review. Clin Ther 1996; 18: 1227–1241.

    Article  CAS  PubMed  Google Scholar 

  2. Grayhack JT, Kozlowski JM, Lee C . The pathogenesis of benign prostatic hyperplasia: a proposed hypothesis and critical evaluation. J Urol 1998; 160: 2375–2380.

    Article  CAS  PubMed  Google Scholar 

  3. McNeal J . Pathology of benign prostatic hyperplasia. Insight into etiology. Urol Clin N Am 1990; 17: 477–486.

    CAS  Google Scholar 

  4. Claus S, Berges R, Senge T, Schulze H . Cell kinetics in epithelium and stroma of benign prostatic hyperplasia. J Urol 1997; 158: 217–221.

    Article  CAS  PubMed  Google Scholar 

  5. Colombel M et al. Zonal variation of apoptosis and proliferation in the normal prostate and in benign prostatic hyperplasia. Br J Urol 1998; 82: 380–385.

    Article  CAS  PubMed  Google Scholar 

  6. Kyprianou N, Huacheng T, Jacobs SC . Apoptotic vs proliferative activities in human benign prostatic hyperplasia. Hum Pathol 1996; 27: 668–675.

    Article  CAS  PubMed  Google Scholar 

  7. Limas C, Frizelle SP . Proliferative activity in benign and neoplastic prostatic epithelium. J Pathol 1994; 74: 201–208.

    Article  Google Scholar 

  8. Cardillo M et al. Resistance to apoptosis and up regulation of BCL2 in benign prostatic hyperplasia after androgen deprivation. J Urol 1997; 158: 212–216.

    Article  CAS  PubMed  Google Scholar 

  9. Rakozy C et al. Expression of BCL2, p53 and p21 in benign and malignant prostatic tissue before and after radiation therapy. Mod Pathol 1998; 11: 892–899.

    CAS  PubMed  Google Scholar 

  10. Gandour-Edwards R, Huang A, Dietch A, deVere-White R . Immunolocalization of BCL2 in benign prostatic epithelium. An evaluation of the effects of androgen ablation. J Urol Pathol 1998; 7: 157–165.

    Google Scholar 

  11. Basu A, Haldar S . The relationship between BCL2, BAX and p53: consequences for cell cycle progression and cell death. Mol Hum Reprod 1998; 4: 1089–1109.

    Article  Google Scholar 

  12. Vang E, Korsmeyer SJ . Molecular thanatopsis: a discourse on the BCL2 family and cell death. Blood 1996; 88: 386–401.

    Google Scholar 

  13. Oltvai ZN, Milliman CL, Korsmeyer SJ . Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax that accelerates programmed cell death. Cell 1993; 74: 609–619.

    Article  CAS  PubMed  Google Scholar 

  14. Perlman H et al. An elevated bax/bcl-2 ratio corresponds with the onset of prostate epithelial cell apoptosis. Cell Death Diff 1999; 6: 48–54.

    Article  CAS  Google Scholar 

  15. Bruckheimer EM et al. The impact of bcl-2 expression and bax deficiency on prostate homeostasis in vivo. Oncogene 2000; 19: 2404–2412.

    Article  CAS  PubMed  Google Scholar 

  16. Nakayama K et al. Mice lacking p27(Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 1996; 85: 707–720.

    Article  CAS  PubMed  Google Scholar 

  17. Guo Y, Sklar GN, Borkowski A, Kyprianou N . Loss of the cyclin–dependent kinase inhibitor p27 (Kip1) protein in human prostate cancer correlates with tumor grade. Clin Cancer Res 1997; 12 (Part 1): 2269–2274.

    Google Scholar 

  18. Cordon-Cardo C et al. Distinct altered patterns of p27 gene expression in benign prostatic hyperplasia and prostatic carcinoma. J Natl Cancer Inst 1998; 90: 1284–1291.

    Article  CAS  PubMed  Google Scholar 

  19. Brooks JD et al. CG island methylation changes near the GSTP1 gene in prostatic intraepithelial neoplasia. Cancer Epidemiol Biomarkers Prev 1998; 7: 531–536.

    CAS  PubMed  Google Scholar 

  20. Pardo FS, Su M, Borek C . Cyclin D1 induced apoptosis maintains the integrity of the G1/S checkpoint following ionizing radiation irradiation. Somat Cell Mol Genet 1996; 22: 135–144.

    Article  CAS  PubMed  Google Scholar 

  21. Collins K, Jacks T, Pavaletich N . The cell cycle and cancer. Proc Natl Acad Sci, USA 1997; 94: 2776–2778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kyprianou N et al. Induction of prostate apoptosis by doxazosin in benign prostatic hyperplasia. J Urol 1998; 159: 1810–1815.

    Article  CAS  PubMed  Google Scholar 

  23. Chon JK et al. α-adrenoreceptor antagonists terazosin and doxazosin induce prostate apoptosis without affecting cell proliferation in patients with benign prostatic hyperplasia. J Urol 1999; 161: 2002–2008.

    Article  CAS  PubMed  Google Scholar 

  24. Kishi H et al. Expression of the survivin gene in prostate cancer: correlation with clinicopathological characteristics, proliferative activity and apoptosis. J Urol 2004; 171: 1855–1860.

    Article  CAS  PubMed  Google Scholar 

  25. Drobnjak M et al. Altered expression of p27 and Skp2 proteins in prostate cancer of African-American patients. Clin Cancer Res 2003; 9: 2613–2619.

    CAS  PubMed  Google Scholar 

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Acknowledgements

Our work was supported by a grant from the National Institute for Aging (AG15404).

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Correspondence to R Gandour-Edwards.

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Gandour-Edwards, R., Mack, P., deVere-White, R. et al. Abnormalities of apoptotic and cell cycle regulatory proteins in distinct histopathologic components of benign prostatic hyperplasia. Prostate Cancer Prostatic Dis 7, 321–326 (2004). https://doi.org/10.1038/sj.pcan.4500749

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