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p63 Cytoplasmic Aberrance is Associated with High Prostate Cancer Stem Cell Expression

  • 발행 : 2012.05.30

초록

Introduction: Prostate cancer in Indonesia is the $3^{rd}$ ranking cancer among males and the $5^{th}$ rank for their cancer mortality. Prognostic markers that can identify aggressive prostate cancer in early stages and help select appropriate therapy to finally reduce the mortality are therefore urgently needed. It has been suggested that stem cells in the prostate gland have a role in initiation, progression, and metastasis of cancer, although controversy continues to exist. Maintenance of normal stem cell or reserve cell populations in several epithelia including prostate has been shown to be regulated by p63 and alteration of p63 expression is considered to have an oncogenic role in prostate cancer. We hypothesize that the expression of cytoplasmic aberrance of p63 is associated with high ALDH1A1 expression as a cancer stem cell marker, thus leading to progression of prostate cancer. Methods: Using a cross-sectional study during two years (2009-2010), a total of 79 paraffin embedded tissues of benign prostatic hyperplasia, PIN prostatic intraepithelial neoplasia, low and high Gleason score prostate cancer were investigated using immunohistochemistry. Associations between cytoplasmic p63 and ALDH1A1, as well as with pathological diagnosis, were analyzed by Chi-Square test using SPSS 15.0. Links of both markers with cell proliferation rate (KI-67) and apoptotic rate (cleaved caspase 3) were also analyzed by Kruskal-Wallis test. Results: The mean age of patient at the diagnosis is 70.0 years. Cytoplasmic aberrance of p63 was associated with ALDH1A1 expression (p<0.001) and both were found to have significant relationships with pathological diagnosis (including Gleason score), (p=0.006 and p<0.001 respectively). Moreover, it was also found that higher levels of cytoplasmic p63 were significantly associated with the frequency of proliferating cells and cells undergoing apoptosis in prostate cancers (p=0.001 and p=0.016 respectively). Conclusion: p63 cytoplasmic aberrance is associated with high ALDH1A1 expression. These components are suggested to have an important role in prostate cancer progression and may be used as molecular markers.

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참고문헌

  1. Aihara M, Truong LD, Dunn JK, et al (1994). Frequency of apoptotic bodies positively correlates with Gleason score in prostate cancer. Hum Pathol, 25, 797-801. https://doi.org/10.1016/0046-8177(94)90249-6
  2. Boldrup L, Coates PJ, Gu X, Nylander (2007). $\Delta$Np63 isoforms regulate CD44 and keratins 4, 6, 14 and 19 in squamous cell carcinoma of head and neck. J Pathol, 213, 384-91. https://doi.org/10.1002/path.2237
  3. Carroll DK, Carroll JS, Leong CO, et al (2006). p63 regulates an adhesion programme and cell survival in epithelial cells. Nat Cell Biol, 8, 551-61 https://doi.org/10.1038/ncb1420
  4. Chute JP, Muramoto GG, Whitesides J, et al (2006). Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells. Proc Natl Acad Sci USA, 31, 11707-12.
  5. Cookson MS, Aus G, Burnett AL, et al (2007). Variation in the definition of biochemical recurrence in patients treated for localized prostatecancer: the American urological association prostate guidelines for localized prostate cancer update panel report and recommendations for a standard in the reporting of surgical outcomes. J Urol, 177, 540-5. https://doi.org/10.1016/j.juro.2006.10.097
  6. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005). Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res, 65, 10946-51. https://doi.org/10.1158/0008-5472.CAN-05-2018
  7. Dachille G, Cai T, Ludovicoi GM, et al (2008). Prognostic role of cell apoptotic rate in prostate cancer: Outcome of a longtime follow-up study. Oncology reports, 19, 541-5.
  8. Dhillon PK, Barry M, Stampfer MJ, et al (2009). Aberrant cytoplasmic expression of p63 and prostate cancer mortality. Cancer Epidemiol Biomarkers Prev, 18, 595-600. https://doi.org/10.1158/1055-9965.EPI-08-0785
  9. Di Como CJ, Urist MJ, Babayan I, et al (2002). p63 expression profiles in human normal and tumor tissues. Clin Cancer Res, 8, 494-501.
  10. Dohn M, zhang S, Chen X (2001). p63alpha and DeltaNp63alpha can induce cell cycle arrest and apoptosis and differentially regulate p53 target genes. Oncogene, 20, 3193-205. https://doi.org/10.1038/sj.onc.1204427
  11. Du Z, Li J, Wang L, et al (2010). Overexpression of ${\Delta}Np63{\alpha}$ induces a stem cell phenotype in MCF7 breast carcinoma cell line through the Notch pathway. Cancer Sci, 101, 2417-24. https://doi.org/10.1111/j.1349-7006.2010.01700.x
  12. Duester G (2000). Families of retinoid dehydrogenases regulating vitamin A function: production of visual pigment and retinoic acid. Eur J Biochem, 267, 4315-24. https://doi.org/10.1046/j.1432-1327.2000.01497.x
  13. Eble JN, sauter G, Epstein JI, Sesterhenn IA (2004). Pathology and genetics of tumours of the urinary sytem and male genital organs. IARC Press. Lyon.
  14. Ferlay J, Shin HR, Bray F, et al (2001). GLOBOCAN 2008, cancer incidence and mortality worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer. Available from: http://globocan.iarc.fr.
  15. Ginestier C, Hur MH, Charafe-Jauffret E, et al (2007). ALDH1 is a marker of normal and malignant human mammry stem cells and predictor of poor clinical outcome. Cell Stem Cell, 1, 555-67. https://doi.org/10.1016/j.stem.2007.08.014
  16. Humphrey PA (2004). Gleason grading and prognostic factors in carcinoma of the prostate. Modern Pathology, 17, 292-306 https://doi.org/10.1038/modpathol.3800054
  17. Landen CN, Goodman B, Katre1 AA, et al (2010). Targeting Aldehyde Dehydrogenase Cancer Stem Cells in Ovarian Cancer. Mol Cancer Ther, 9, 3186-99. https://doi.org/10.1158/1535-7163.MCT-10-0563
  18. Li T, Su Y, Mei Y, et al (2010). ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients' outcome. Lab Invest, 90, 234-44. https://doi.org/10.1038/labinvest.2009.127
  19. Magni M, Shammah S, Schiro R, et al (1996). Induction of cyclophosphamide-resistance by aldehyde-dehydrogenase gene transfer. Blood, 87, 1097-103.
  20. Mills AA, Zheng B, Wang XJ, et al (1999). p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature, 398, 708-13. https://doi.org/10.1038/19531
  21. Narahashi T, Niki T, Wang T, et al (2006). Cytoplasmic localization of p63 is associated with poor patient survival in lung adenocarcinoma. Histopathology, 49, 349-57. https://doi.org/10.1111/j.1365-2559.2006.02507.x
  22. Nylander K, Vojtesek B, Nenutil R, et al (2002). Differential expression of p63 isoforms in normal tissues and neoplastic cells. J Pathol, 198, 417-27. https://doi.org/10.1002/path.1231
  23. Pardal R, Clarke MF, Morrison SJ (2003). Applying the principles of stem-cell biology to cancer. Nat Rev Cancer, 3, 895-902. https://doi.org/10.1038/nrc1232
  24. Patrawala L, Calhoun T, Schneider-Broussard R, et al (2006). Highly purified CD44(+) prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene, 25, 1696-708. https://doi.org/10.1038/sj.onc.1209327
  25. Reiner T, De las Pozas A, Parrondo R, Perez-Stable C (2007). Progression of prostate cancer from a subset of p63-positive basal epithelial cells in FG/Tag transgenic mice. Mol Cancer Res, 5, 1171-9. https://doi.org/10.1158/1541-7786.MCR-07-0024
  26. Senoo M, Pinto F, Crum CP, McKeon F (2007). p63 Is Essential for the Proliferative Potential of Stem Cells in Stratified Epithelia. Cell, 129, 523-36. https://doi.org/10.1016/j.cell.2007.02.045
  27. Signoretti S, Waltregny D, Dilks J, et al (2000). p63 is a prostate basal cell marker and is required for prostate development. Am J Pathol, 157, 1769-75. https://doi.org/10.1016/S0002-9440(10)64814-6
  28. Sophos NA, Vasiliou V (2003). Aldehyde dehydrogenase gene superfamily: the 2002 update. Chem Biol Interact, 143, 5-22. https://doi.org/10.1016/S0009-2797(02)00163-1
  29. Van Den Hoogen C, Van Der Horst G, Cheung H, et al (2010). High aldehyde dehydrogenase activity identifies tumorinitiating and metastasis-initiating cells in human prostate cancer. Cancer Res, 70, 5163-73. https://doi.org/10.1158/0008-5472.CAN-09-3806
  30. Vigneswaran N, Baucum D, Wu J, et al (2007). Repression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but not its receptors during oral cancer progression. BMC Cancer, 7, 108. https://doi.org/10.1186/1471-2407-7-108
  31. Yang A, Kaghad M, Wang Y, et al (1998). p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell, 2, 305-16. https://doi.org/10.1016/S1097-2765(00)80275-0
  32. Yang A, Schweitzer R, Sun D, et al (1999). p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature, 398, 714-8. https://doi.org/10.1038/19539
  33. Yoshida A, Rzhetsky A, Hsu LC, Chang C (1998). Human aldehyde dehydrogenase gene family. Eur J Biochem, 251, 549-57. https://doi.org/10.1046/j.1432-1327.1998.2510549.x
  34. Zucchi I, Astigiano S, Bertalot G, et al (2008). Distinct populations of tumor-initiating cells derived from a tumor generated by rat mammary cancer stem cells. Proc Natl Acad Sci U S A, 105, 16940-5. https://doi.org/10.1073/pnas.0808978105

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