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p63 regulates cell proliferation and cell cycle progression‑associated genes in stromal cells of giant cell tumor of the bone

  • Authors:
    • Carol Po Ying Lau
    • Patrick Kwok Shing Ng
    • Man Shan Li
    • Stephen Kwok Wing Tsui
    • Lin Huang
    • Shekhar Madhukar Kumta
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR, P.R. China, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR, P.R. China, Division of Plastic, Reconstructive and Aesthetic Surgery, Department of Surgery, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR, P.R. China
    Copyright: © Lau et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 437-443
    |
    Published online on: December 3, 2012
       https://doi.org/10.3892/ijo.2012.1727
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Abstract

Giant cell tumor of bone (GCT) is a destructive neoplasm of uncertain etiology that affects the epiphyseal ends of long bones in young adults. GCT stromal cells (GCTSCs) are the primary neoplastic cells of this tumor and are the only proliferating cell component in long-term culture, which recruits osteoclast-like giant cells that eventually mediate bone destruction. The oncogenesis of GCT and factors driving the neoplastic stromal cells to proliferate extensively and pause at an early differentiation stage of pre-osteoblast lineage remain unknown. Overexpression of p63 was observed in GCTSCs and there is growing evidence that p63 is involved in oncogenesis through different mechanisms. This study aimed to understand the specific role of p63 in cell proliferation and oncogenesis of GCTSCs. We confirmed p63 expression in the mononuclear cells in GCT by immunohistochemical staining. By real-time PCR analysis, we showed a higher level (>15‑fold) of TAp63 expression in GCTSCs compared to that in mesenchymal stem cells. Furthermore, we observed that knockdown of the p63 gene by siRNA transfection greatly reduced cell proliferation and induced cell cycle arrest at S phase in GCTSCs. We found that the mRNA expression of CDC2 and CDC25C was substantially suppressed by p63 knockdown at 24-72 h. Moreover, p63 was found to be recruited on the regulatory regions of CDC2 and CDC25C, which contain p53-responsive elements. In summary, our data suggest that p63 regulates GCTSC proliferation by binding to the CDC2 and CDC25C p53-REs, which may inhibit the p53 tumor suppressor activity and contribute to GCT tumorigenesis.
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1. 

Goldring SR, Schille AL, Mankin HJ, Dayer JM and Krane SM: Characterization of cells from human giant cell tumors of bone. Clin Orthop Relat Res. 204:59–75. 1986.PubMed/NCBI

2. 

Zheng MH, Robbins P, Xu J, Huang L, Wood DJ and Papadimitriou JM: The histogenesis of giant cell tumor of bone: a model of interaction between neoplastic cells and osteoclasts. Histol Histopathol. 16:297–307. 2001.PubMed/NCBI

3. 

Huang L, Teng XY, Cheng YY, Lee KM and Kumta SM: Expression of preosteoblast markers and Cbfa-1 and Osterix gene transcripts in stromal tumor cells of giant cell tumor of bone. Bone. 34:393–401. 2004. View Article : Google Scholar : PubMed/NCBI

4. 

Sciot R, Dorfman H, Brys P, et al: Cytogenetic-morphologic correlations in aneurismal bone cyst, giant cell tumor of bone and combined lesions. Mod Pathol. 13:1206–1210. 2000. View Article : Google Scholar : PubMed/NCBI

5. 

Schwartz HS, Eskew JD and Butler MG: Clonality studies in giant cell tumor of bone. J Orthop. 20:387–390. 2002.PubMed/NCBI

6. 

Sawyer JR, Goosen LS, Binz RL, Swanson CM and Nicholas RW: Evidence for telomeric fusions as a mechanism for recurring structural aberrations of chromosome 11 in giant cell tumor of bone. Cancer Genet Cytogenet. 159:32–36. 2005. View Article : Google Scholar : PubMed/NCBI

7. 

Forsyth RG, Boeck G, Bekaert S, et al: Telomere biology in giant cell tumour of bone. J Pathol. 214:555–563. 2008. View Article : Google Scholar : PubMed/NCBI

8. 

Lee CH, Espinosa I, Jensen KC, et al: Gene expression profiling identified p63 as a diagnostic marker for giant cell tumor of the bone. Mod Pathol. 21:531–539. 2008. View Article : Google Scholar : PubMed/NCBI

9. 

Dickson BC, Li SQ, Wunder JS, et al: Giant cell tumor of bone express p63. Mod Pathol. 21:369–375. 2008. View Article : Google Scholar : PubMed/NCBI

10. 

Müller M, Schleithoff ES, Stremmel W, Melino G, Krammer PH and Schilling T: One, two, three-p53, p63, p73 and chemosensitivity. Drug Resist Updat. 9:288–306. 2006.PubMed/NCBI

11. 

Murray-Zmijewski F, Lane DP and Bourdon JC: p53/p63/p73 isoforms: an orchestra of isoforms to harmonize cell differentiation and response to stress. Cell Death Differ. 13:962–972. 2006. View Article : Google Scholar : PubMed/NCBI

12. 

Ghioni P, Bolognese F, Duijf PH, Van Bokhoven H, Mantovani R and Guerrini L: Complex transcriptional effects of p63 isoforms: identification of novel activation and repression domains. Mol Cell Biol. 22:8659–8668. 2002. View Article : Google Scholar : PubMed/NCBI

13. 

Mangiulli M, Valletti A, Caratozzolo MF, Tullo A, Sbisà E, Pesole G and D’Erchia AM: Identification and functional characterization of two new transcriptional variants of the human p63 gene. Nucleic Acids Res. 37:6092–6104. 2009. View Article : Google Scholar : PubMed/NCBI

14. 

Moll UM and Slade N: p63 and p73: roles in development and tumor formation. Mol Cancer Res. 2:371–386. 2004.PubMed/NCBI

15. 

Hermanns P and Lee B: Transcriptional dysregulation in skeletal malformation syndromes. Am J Med Genet. 106:258–271. 2001. View Article : Google Scholar : PubMed/NCBI

16. 

Lau CP, Huang L, Tsui SK, Ng PK, Leung PY and Kumta SM: Pamidronate, farnesyl transferase, and geranylgeranyl transferase-I inhibitors affects cell proliferation, apoptosis, and OPG/RANKL mRNA expression in stromal cells of giant cell tumor of bone. J Orthop Res. 29:403–413. 2011. View Article : Google Scholar

17. 

Wulling M, Delling G and Kaiser E: The origin of the neoplastic stromal cell in giant cell tumor of bone. Hum Pathol. 34:983–993. 2003.PubMed/NCBI

18. 

Robinson D, Segal M and Nevo Z: Giant cell tumor of bone. The role of fibroblast growth factor 3 positive mesenchymal stem cells in its pathogenesis. Pathobiology. 70:333–342. 2002.PubMed/NCBI

19. 

Lefkimmiatis K, Caratozzolo MF, Merlo P, et al: p73 and p63 sustain cellular growth by transcriptional activation of cell cycle progression genes. Cancer Res. 69:8563–8571. 2009. View Article : Google Scholar : PubMed/NCBI

20. 

Malaguarnera R, Mandarino A, Mazzon E, et al: The p53-homologue p63 may promote thyroid cancer progression. Endocr Relat Cancer. 12:953–971. 2005. View Article : Google Scholar : PubMed/NCBI

21. 

Rocco JW, Leong CO, Kuperwasser N, DeYoung MP and Ellisen LW: p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis. Cancer cell. 9:45–56. 2006. View Article : Google Scholar : PubMed/NCBI

22. 

Sbisà E, Mastropasqua G, Lefkimmiatis K, Caratozzolo MF, D’Erchia AM and Tullo A: Connecting p63 to cellular proliferation: the example of the adenosine deaminase target gene. Cell Cycle. 5:205–212. 2006.PubMed/NCBI

23. 

Crook T, Nicholls JM, Brooks L, O’Nions J and Allday MJ: High level expression of deltaN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma. Oncogene. 19:3439–3444. 2000. View Article : Google Scholar : PubMed/NCBI

24. 

Senoo M, Tsuchiya I, Matsumura Y, et al: Transcriptional dysregulation of the p73L/p63/ p51/p40/KET gene in human squamous cell carcinomas: expression of Delta Np73L a novel dominant-negative isoform and loss of expression of the potential tumor suppressor p51. Br J Cancer. 84:1235–1241. 2001. View Article : Google Scholar

25. 

Hibi K, Trink B, Patturajan M, et al: AIS is an oncogene amplified in squamous cell carcinoma. Proc Natl Acad Sci USA. 97:5462–5467. 2000. View Article : Google Scholar : PubMed/NCBI

26. 

Park BJ, Lee SJ, Kim JI, et al: Frequent alteration of p63 expression in human primary bladder carcinomas. Cancer Res. 60:3370–3374. 2000.PubMed/NCBI

27. 

Taniere P, Martel-Planche G, Saurin JC, Lombard-Bohas C, Berger F, Scoazec JY and Hainaut P: TP53 mutations amplification of P63 and expression of cell cycle proteins in squamous cell carcinoma of the oesophagus from a low incidence area in Western Europe. Br J Cancer. 85:721–726. 2001. View Article : Google Scholar : PubMed/NCBI

28. 

Zaika AI, Kovalev S, Marchenko ND and Moll UM: Overexpression of the wild-type p73 gene in breast cancer tissues and cell lines. Cancer Res. 59:3257–3263. 1999.PubMed/NCBI

29. 

Zaika AI, Slade N, Erster SH, et al: DeltaNp73, a dominant-negative inhibitor of wild-type p53 and TAp73, is up regulated in human tumors. J Exp Med. 196:765–780. 2002. View Article : Google Scholar : PubMed/NCBI

30. 

Tannapfel A, Schmelzer S, Benicke M, et al: Expression of the p53 homologues p63 and p73 in multiple simultaneous gastric cancer. J Pathol. 195:163–170. 2001. View Article : Google Scholar : PubMed/NCBI

31. 

Wong KC, Kumta SM, Tse LF, Ng EW and Lee KS: Navigation Endoscopic Assisted Tumor (NEAT) surgery for benign bone tumors of the extremities. Comput Aided Surg. 15:32–39. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Lau CP, Ng PK, Li MS, Tsui SK, Huang L and Kumta SM: p63 regulates cell proliferation and cell cycle progression‑associated genes in stromal cells of giant cell tumor of the bone. Int J Oncol 42: 437-443, 2013.
APA
Lau, C.P., Ng, P.K., Li, M.S., Tsui, S.K., Huang, L., & Kumta, S.M. (2013). p63 regulates cell proliferation and cell cycle progression‑associated genes in stromal cells of giant cell tumor of the bone. International Journal of Oncology, 42, 437-443. https://doi.org/10.3892/ijo.2012.1727
MLA
Lau, C. P., Ng, P. K., Li, M. S., Tsui, S. K., Huang, L., Kumta, S. M."p63 regulates cell proliferation and cell cycle progression‑associated genes in stromal cells of giant cell tumor of the bone". International Journal of Oncology 42.2 (2013): 437-443.
Chicago
Lau, C. P., Ng, P. K., Li, M. S., Tsui, S. K., Huang, L., Kumta, S. M."p63 regulates cell proliferation and cell cycle progression‑associated genes in stromal cells of giant cell tumor of the bone". International Journal of Oncology 42, no. 2 (2013): 437-443. https://doi.org/10.3892/ijo.2012.1727
Copy and paste a formatted citation
x
Spandidos Publications style
Lau CP, Ng PK, Li MS, Tsui SK, Huang L and Kumta SM: p63 regulates cell proliferation and cell cycle progression‑associated genes in stromal cells of giant cell tumor of the bone. Int J Oncol 42: 437-443, 2013.
APA
Lau, C.P., Ng, P.K., Li, M.S., Tsui, S.K., Huang, L., & Kumta, S.M. (2013). p63 regulates cell proliferation and cell cycle progression‑associated genes in stromal cells of giant cell tumor of the bone. International Journal of Oncology, 42, 437-443. https://doi.org/10.3892/ijo.2012.1727
MLA
Lau, C. P., Ng, P. K., Li, M. S., Tsui, S. K., Huang, L., Kumta, S. M."p63 regulates cell proliferation and cell cycle progression‑associated genes in stromal cells of giant cell tumor of the bone". International Journal of Oncology 42.2 (2013): 437-443.
Chicago
Lau, C. P., Ng, P. K., Li, M. S., Tsui, S. K., Huang, L., Kumta, S. M."p63 regulates cell proliferation and cell cycle progression‑associated genes in stromal cells of giant cell tumor of the bone". International Journal of Oncology 42, no. 2 (2013): 437-443. https://doi.org/10.3892/ijo.2012.1727
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