High-Expression of PTEN and an Absence of PCNA in Osteoclast-Like Multinucleated Giant Cells of Giant Cell Tumors in Bone

Authors

  • Chao Lou Department of Genetics, Maternal and Children Healthcare Hospital of Shaanxi Province, Xi’an, 710003, China
  • Rong Qiang Department of Genetics, Maternal and Children Healthcare Hospital of Shaanxi Province, Xi’an, 710003, China
  • Hongmin Yan Department of Genetics, Maternal and Children Healthcare Hospital of Shaanxi Province, Xi’an, 710003, China
  • Jie Li Department of Genetics, Maternal and Children Healthcare Hospital of Shaanxi Province, Xi’an, 710003, China

DOI:

https://doi.org/10.6000/1929-2279.2012.01.01.17

Keywords:

PTEN, giant cell tumor, bone, large cell.

Abstract

 Giant cell tumors (GCTs) found in bone are so named for the conspicuous presence of numerous osteoclast-like multinucleated giant cells (OLMGCs). Although GCT studies have revealed that the OLMGCs are the cells responsible for tumor formation, these cells continue to receive a good deal of research attention. The tumor -suppressor gene, PTEN, is known to be involved in various malignancies. Recently, however, PTEN has been reported to be important for neuron enlargement and cardiomyocyte hypertrophy. Given the role of PTEN in both carcinomas as well as cell hypertrophy, we sought to elucidate the relationship between PTEN and OLMGCs. In this study, we confirmed the existence of PTEN in GCTs in bone using PCR. In particular, exons-3,4 and 5 of the PTEN gene was detected. Exons-3,4,5 of PTEN gene were found by PCR in all of 8 cases. Single cells microdissection was used to isolate OLMGCs from GCTs and verify the existence of the PTEN gene in the osteoclast-like multinucleated giant cells through PCR amplication of PTEN exon-3. Exon-3 of PTEN were detected by PCR in 5 of the 10 microdissected samples. PTEN mRNA expression was detected by in situ hybridization and the expressions of PTEN protein and proliferating cell nuclear antigen (PCNA) in GCTs were detected by immunohistochemistry. High expression levels of PTEN mRNA was detected only in OLMGCs in 23 of 27 GCT cases. Likewise,high expression of PTEN protein was also found only in OLMGCs in 21 of the 27 GCT cases and the giant cells did not express PCNA. In contrast, the neoplastic stromal cells with high PCNA labeling were almost always PTEN-negative by immunohistochemical staining. These results suggested that high-expression of PTEN in OLMGCs may involve in the formation size of GCTs.

References

Abbott RT, Tripp S, Perkins SL, Elenitoba-Johnson KS, Lim MS. Analysis of the PI-3-Kinase-PTEN-AKT pathway in human lymphoma and leukemia using a cell line microarray. Mod Pathol 2003; 16: 607-12. http://dx.doi.org/10.1097/01.MP.0000067423.83712.74

Masui F, Ushigome S, Fujii K. Giant cell tumor of bone: an immunohistochemical comparative study. Pathol Int 1998; 48: 355-61. http://dx.doi.org/10.1111/j.1440-1827.1998.tb03918.x

Wulling M, Delling G, Kaiser E. The origin of the neoplastic stromal cell in giant cell tumor of bone. Hum Pathol 2003; 34: 83-93.

Waite KA, Eng C. Protean PTEN: Form and Function Am J Hum Genet 2002; 70: 829-44. http://dx.doi.org/10.1086/340026

Fenic I, Franke F, Failing K, Steger K, Woenckhaus J. Expression of PTEN in malignant and non-malignant human prostate tissues: comparison with p27 protein expression. J Pathol 2004; 203: 559-66. http://dx.doi.org/10.1002/path.1545

Karoui M, Tresallet C, Julie C, et al. Loss of heterozygosity on 10q and mutational status of PTEN and BMPR1A in colorectal primary tumours and metastases. Br J Cancer 2004; 90: 1230-4. http://dx.doi.org/10.1038/sj.bjc.6601687

Pilarski R, Eng C. Will the real Cowden syndrome please stand up (again)? Expanding mutational and clinical spectra of the PTEN hamartoma tumour syndrome. J Med Genet 2004; 41: 323-26. http://dx.doi.org/10.1136/jmg.2004.018036

Torres J, Navarro S, Rogla I, et al. Heterogeneous lack of expression of the tumour suppressor PTEN protein in human neoplastic tissues. Eur J Cancer 2001; 37: 114-21. http://dx.doi.org/10.1016/S0959-8049(00)00366-X

Simpson L, Parsons R. PTEN: life as a tumour suppressor. Exp Cell Res 2001; 264: 29-41. http://dx.doi.org/10.1006/excr.2000.5130

Backman SA, Stambolic V, Suzuki A, et al. Deletion of PTEN in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease. Nat Genet 2001; 29: 396-403. http://dx.doi.org/10.1038/ng782

Kwon CH, Zhu X, Zhang J, et al. PTEN regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease. Nat Genet 2001; 29: 40411. http://dx.doi.org/10.1038/ng781

Crackower MA, Oudit GY, Kozieradzki I, et al. Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways. Cell 2002; 110: 737-49. http://dx.doi.org/10.1016/S0092-8674(02)00969-8

Backman S, Stambolic V, Mak T. PTEN function in mammalian cell size regulation. Curr Opin Neurobiol 2002; 12: 516-522. http://dx.doi.org/10.1016/S0959-4388(02)00354-9

Lee C, Kim JS, Waldman T. PTEN gene targeting reveals a radiation-induced size checkpoint in human cancer cells. Cancer Res 2004; 64: 6906-14. http://dx.doi.org/10.1158/0008-5472.CAN-04-1767

Kwon CH, Zhu X, Zhang J, Baker SJ. mTor is required for hypertrophy of Pten-deficient neuronal soma in vivo. Proc Natl Acad Sci USA 2003; 100: 12923-8. http://dx.doi.org/10.1073/pnas.2132711100

Stocker H, Hafen E. Genetic control of cell size. Curr Opin Genet Dev 2000; 10: 529-35. http://dx.doi.org/10.1016/S0959-437X(00)00123-4

Sulis ML, Parsons R. PTEN: from pathology to biology. Trends Cell Biol 2003; 13: 478-83. http://dx.doi.org/10.1016/S0962-8924(03)00175-2

Gross-Bellard M, Oudet P, Chambon P. Isolation of high-molecular-weight DNA from mammalian cells. Eur J Biochem 1973; 36: 32-8. http://dx.doi.org/10.1111/j.1432-1033.1973.tb02881.x

Kriegsmann J, Keyszer GM, Geiler T, Brauer R, Gay RE, Gay S. Expression of vascular cell adhesion molecule-1 mRNA and protein in rheumatoid synovium demonstrated by in situ hybridization and immunohistochemistry. Lab Invest 1995; 72: 209-14.

Anthony R, Bharat J, Andre JB, et al. Study of interlaboratory reliability and reproducibility of Estrogen and Progesterone receptor assays in Europe. Am J Clin Phathol 2001; 115: 44-58. http://dx.doi.org/10.1309/H905-HYC1-6UQQ-981P

Sternberg SS, Antonioli DA, Cater D, Mills SE, Oberman HA. Diagnostic Surgical Pathology, Volume 1, Fourth Edition 2004.

Garcia JM, Silva J, Pena C, et al. Promoter methylation of the PTEN gene is a common molecular change in breast cancer. Genes Chromosomes Cancer 2004; 41: 117-24. http://dx.doi.org/10.1002/gcc.20062

Khan S, Kumagai T, Vora J, et al. PTEN promoter is methylated in a proportion of invasive breast cancers. Int J Cancer 2004; 112: 407-10. http://dx.doi.org/10.1002/ijc.20447

Cantley LC, Neel BG. New insights into tumor suppression: PTEN suppresses tumour formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci USA 1999; 96: 4240-5. http://dx.doi.org/10.1073/pnas.96.8.4240

Brader S, Eccles SA. Phosphoinositide 3-kinase signalling pathways in tumor progression, invasion and angiogenesis. Tumori 2004; 90: 2-8.

Stambolic V, Suzuki A, de la Pompa JL, et al. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 1998; 95: 29-39. http://dx.doi.org/10.1016/S0092-8674(00)81780-8

de Souza PE, Paim JF, Carvalhais JN, Gomez RS. Immunohistochemical expression of p53, MDM2, Ki-67 and PCNA in central giant cell granuloma and giant cell tumor. J Oral Pathol Med 1999; 28: 54-8. http://dx.doi.org/10.1111/j.1600-0714.1999.tb01996.x

Masui F, Ushigome S, Fujii K. Giant cell tumor of bone: a clinicopathologic study of prognostic factors. Pathol Int 1998; 48: 723-9. http://dx.doi.org/10.1111/j.1440-1827.1998.tb03973.x

Robinson D, Lewis MM, Nevo Z, Kenan S, Einhom TA. The radiographic stage of giant cell tumor related to stromal cells' proliferation. Tissue cultures in 13 cases. Acta Orthop Scand 1997; 68: 294-7. http://dx.doi.org/10.3109/17453679708996705

Sun H, Lesche R, Li DM. PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway. Proc Natl Acad Sci USA 1999; 96: 6199-204. http://dx.doi.org/10.1073/pnas.96.11.6199

Furnari FB, Huang HJ, Cavenee WK. The phosphoinositol phosphatase activity of PTEN mediates a serum-sensitive G1 growth arrest in glioma cells. Cancer Res 1998; 58: 5002-8.

Gao X, Neufeld TP, Pan D. Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways. Dev Biol 2000; 221: 404-18. http://dx.doi.org/10.1006/dbio.2000.9680

Downloads

Published

2012-01-28

How to Cite

Chao Lou, Rong Qiang, Hongmin Yan, & Jie Li. (2012). High-Expression of PTEN and an Absence of PCNA in Osteoclast-Like Multinucleated Giant Cells of Giant Cell Tumors in Bone . Journal of Cancer Research Updates, 1(1),  114–121. https://doi.org/10.6000/1929-2279.2012.01.01.17

Issue

Section

Articles