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Expression of pituitary tumor transforming gene (PTTG) in human pituitary macroadenomas

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Tumor Biology

Abstract

The purpose of this study was to elucidate the relationship between pituitary tumor transforming gene (PTTG) and invasiveness in pituitary macroadenomas and to determine the association between PTTG and both the tumor proliferative activity marker proliferation cell nuclear antigen (PCNA) and the angiogenic factor basic fibroblast growth factor. A total of 70 patients with pituitary adenomas who underwent transsphenoidal or craniotomy surgical resection were enrolled. The average age were 42.5 ± 13.7 years (17–64 years) for the invasive group and 46.8 ± 12.1 years (16–71 years) for the non-invasive group, with no significant difference (P = 0.179) between the two groups. RT-PCR analysis of a group of pituitary macroadenomas demonstrated that the expression levels of PTTG and PCNA in invasive pituitary adenomas were significantly higher than in non-invasive pituitary adenomas. Both factors are both closely related to the invasive growth of pituitary adenomas and may possibly serve as important markers of this growth. In conclusion, PTTG may promote invasive tumor growth by stimulating pituitary adenomas proliferation. The mechanisms of tumor growth promotion and invasion of the surrounding structures by PTTG need to be further explored.

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References

  1. Blevins Jr LS, Verity DK, Allen G. Aggressive pituitary tumors. Oncology (Williston Park, NY). 1998;12:1307–12. 15; discussion 15–8.

    Google Scholar 

  2. Buchfelder M. Management of aggressive pituitary adenomas: current treatment strategies. Pituitary. 2009;12:256–60.

    Article  PubMed  Google Scholar 

  3. Dinh JQ, Mahajan A, Palmer MB, Grosshans DR. Particle therapy for central nervous system tumors in pediatric and adult patients. Transl Cancer Res. 2012;1:137–49.

    Google Scholar 

  4. Figarella-Branger D, Trouillas J. The new WHO classification of human pituitary tumors: comments. Acta Neuropathologica. 2006;111:171–2.

    Article  Google Scholar 

  5. Tan J, Chen B, He L, Tang Y, Jiang Z, Yin G, et al. Anacardic acid (6-pentadecylsalicylic acid) induces apoptosis of prostate cancer cells through inhibition of androgen receptor and activation of p53 signaling. Chin J Cancer Res. 2012;24:275–83.

    Article  PubMed  Google Scholar 

  6. Grossman AB. The 2004 World Health Organization classification of pituitary tumors: is it clinically helpful? Acta Neuropathologica. 2006;111:76–7.

    Article  PubMed  Google Scholar 

  7. Kontogeorgos G. Predictive markers of pituitary adenoma behavior. Neuroendocrinology. 2006;83:179–88.

    Article  PubMed  CAS  Google Scholar 

  8. Zhang X, Horwitz GA, Heaney AP, et al. Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab. 1999;84:761–7.

    Article  PubMed  CAS  Google Scholar 

  9. Shimon I, Hinton DR, Weiss MH, Melmed S. Prolactinomas express human heparin-binding secretory transforming gene (hst) protein product: marker of tumour invasiveness. Clin Endocrinol. 1998;48:23–9.

    Article  CAS  Google Scholar 

  10. Hsu DW, Hakim F, Biller BM, et al. Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence. J Neurosurg. 1993;78:753–61.

    Article  PubMed  CAS  Google Scholar 

  11. Jaffrain-Rea ML, Di Stefano D, Minniti G, et al. A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas. Endocrine-Related Cancer. 2002;9:103–13.

    Article  PubMed  CAS  Google Scholar 

  12. Ozer E, Canda MS, Ulukus C, Guray M, Erbayraktar S. Expression of Bcl-2, Bax and p53 proteins in pituitary adenomas: an immunohistochemical study. Tumori. 2003;89:54–9.

    PubMed  Google Scholar 

  13. McCabe CJ, Khaira JS, Boelaert K, et al. Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor-2 (FGF-2) in human pituitary adenomas: relationships to clinical tumour behaviour. Clin Endocrinol. 2003;58:141–50.

    Article  CAS  Google Scholar 

  14. Lloyd RV, Scheithauer BW, Kuroki T, Vidal S, Kovacs K, Stefaneanu L. Vascular endothelial growth factor (VEGF) expression in human pituitary adenomas and carcinomas. Endocr Pathol. 1999;10:229–35.

    Article  PubMed  CAS  Google Scholar 

  15. Zhang X, Horwitz GA, Prezant TR, et al. Structure, expression, and function of human pituitary tumor-transforming gene (PTTG). Mol Endocrinol. 1999;13:156–66.

    Article  PubMed  CAS  Google Scholar 

  16. Salehi F, Kovacs K, Scheithauer BW, Lloyd RV, Cusimano M. Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update. Endocrine-Related Cancer. 2008;15:721–43.

    Article  PubMed  CAS  Google Scholar 

  17. Kim DS, Fong J, Read ML, McCabe CJ. The emerging role of pituitary tumour transforming gene (PTTG) in endocrine tumourigenesis. Mol Cell Endocrinol. 2007;278:1–6.

    Article  PubMed  CAS  Google Scholar 

  18. Bradshaw C, Kakar SS. Pituitary tumor transforming gene: an important gene in normal cellular functions and tumorigenesis. Histol Histopathol. 2007;22:219–26.

    PubMed  CAS  Google Scholar 

  19. Tfelt-Hansen J, Kanuparthi D, Chattopadhyay N. The emerging role of pituitary tumor transforming gene in tumorigenesis. Clinical Medicine & Research. 2006;4:130–7.

    Article  CAS  Google Scholar 

  20. Chesnokova V, Zonis S, Rubinek T, et al. Senescence mediates pituitary hypoplasia and restrains pituitary tumor growth. Cancer Res. 2007;67:10564–72.

    Article  PubMed  CAS  Google Scholar 

  21. Chesnokova V, Kovacs K, Castro AV, Zonis S, Melmed S. Pituitary hypoplasia in Pttg−/− mice is protective for Rb+/− pituitary tumorigenesis. Mol Endocrinol. 2005;19:2371–9.

    Article  PubMed  CAS  Google Scholar 

  22. Heaney AP, Fernando M, Melmed S. Functional role of estrogen in pituitary tumor pathogenesis. J Clin Investig. 2002;109:277–83.

    PubMed  CAS  Google Scholar 

  23. Heaney AP, Horwitz GA, Wang Z, Singson R, Melmed S. Early involvement of estrogen-induced pituitary tumor transforming gene and fibroblast growth factor expression in prolactinoma pathogenesis. Nature Medicine. 1999;5:1317–21.

    Article  PubMed  CAS  Google Scholar 

  24. Chamaon K, Kanakis D, Mawrin C, Dietzmann K, Kirches E. Transcripts of PTTG and growth factors bFGF and IGF-1 are correlated in pituitary adenomas. Experimental and clinical endocrinology & diabetes. German Society of Endocrinology [and] German Diabetes Association. 121;118:121–6.

    Article  Google Scholar 

  25. Minematsu T, Suzuki M, Sanno N, Takekoshi S, Teramoto A, Osamura RY. PTTG overexpression is correlated with angiogenesis in human pituitary adenomas. Endocr Pathol. 2006;17:143–53.

    Article  PubMed  CAS  Google Scholar 

  26. Malik MT, Kakar SS. Regulation of angiogenesis and invasion by human pituitary tumor transforming gene (PTTG) through increased expression and secretion of matrix metalloproteinase-2 (MMP-2). Molecular Cancer. 2006;5:61.

    Article  PubMed  Google Scholar 

  27. Filippella M, Galland F, Kujas M, et al. Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas: a clinical and immunohistochemical study. Clin Endocrinol. 2006;65:536–43.

    Article  Google Scholar 

  28. Wierinckx A, Auger C, Devauchelle P, et al. A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors. Endocrine-Related Cancer. 2007;14:887–900.

    Article  PubMed  CAS  Google Scholar 

  29. Raverot G, Wierinckx A, Dantony E, et al. Prognostic factors in prolactin pituitary tumors: clinical, histological, and molecular data from a series of 94 patients with a long postoperative follow-up. J Clin Endocrinol Metab. 2010;95:1708–16.

    Article  PubMed  CAS  Google Scholar 

  30. Knosp E, Steiner E, Kitz K, Matula C. Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery. 1993;33:610–7. discussion 7–8.

    Article  PubMed  CAS  Google Scholar 

  31. Vieira Jr JO, Cukiert A, Liberman B. Evaluation of magnetic resonance imaging criteria for cavernous sinus invasion in patients with pituitary adenomas: logistic regression analysis and correlation with surgical findings. Surg Neurol. 2006;65:130–5. discussion 5.

    Article  PubMed  Google Scholar 

  32. Vieira Jr JO, Cukiert A, Liberman B. Magnetic resonance imaging of cavernous sinus invasion by pituitary adenoma diagnostic criteria and surgical findings. Arquivos de neuro-psiquiatria. 2004;62:437–43.

    Article  PubMed  Google Scholar 

  33. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001;25:402–8.

    Article  PubMed  CAS  Google Scholar 

  34. Ishikawa H, Heaney AP, Yu R, Horwitz GA, Melmed S. Human pituitary tumor-transforming gene induces angiogenesis. J Clin Endocrinol Metab. 2001;86:867–74.

    Article  PubMed  CAS  Google Scholar 

  35. Edal AL, Skjodt K, Nepper-Rasmussen HJ. SIPAP—a new MR classification for pituitary adenomas. Suprasellar, infrasellar, parasellar, anterior and posterior. Acta radiologica (Stockholm, Sweden: 1987). 1997;38:30–6.

    CAS  Google Scholar 

  36. Hunter JA, Skelly RH, Aylwin SJ, et al. The relationship between pituitary tumour transforming gene (PTTG) expression and in vitro hormone and vascular endothelial growth factor (VEGF) secretion from human pituitary adenomas. European Journal of Endocrinology/European Federation of Endocrine Societies. 2003;148:203–11.

    Article  PubMed  CAS  Google Scholar 

  37. Salehi F, Kovacs K, Scheithauer BW, et al. Immunohistochemical expression of pituitary tumor transforming gene (PTTG) in pituitary adenomas: a correlative study of tumor subtypes. Int J Surg Pathol. 2010;18:5–13.

    Article  PubMed  Google Scholar 

  38. Bravo R, Frank R, Blundell PA, Macdonald-Bravo H. Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature. 1987;326:515–7.

    Article  PubMed  CAS  Google Scholar 

  39. Pawlikowski M, Gruszka A, Kurnatowska I, Winczyk K, Kunert-Radek J, Radek A. Proliferating cell nuclear antigen (PCNA) expression in pituitary adenomas: relationship to the endocrine phenotype of adenoma. Folia histochemica et cytobiologica/Polish Academy of Sciences, Polish Histochemical and Cytochemical Society. 2006;44:37–41.

    PubMed  Google Scholar 

  40. Saeger W, Ludecke B, Ludecke DK. Clinical tumor growth and comparison with proliferation markers in non-functioning (inactive) pituitary adenomas. Experimental and clinical endocrinology & diabetes. German Society of Endocrinology [and] German Diabetes Association. 2008;116:80–5.

    Article  CAS  Google Scholar 

  41. Klencki M, Kurnatowska I, Slowinska-Klencka D, Lewinski A, Pawlikowski M. Correlation between PCNA expression and AgNOR dots in pituitary adenomas. Endocr Pathol. 2001;12:163–9.

    Article  PubMed  CAS  Google Scholar 

  42. Tena-Suck ML, Ortiz-Plata A, de la Vega HA. Phosphatase and tensin homologue and pituitary tumor-transforming gene in pituitary adenomas. Clinical–pathologic and immunohistochemical analysis. Ann Diagn Pathol. 2008;12:275–82.

    Article  PubMed  Google Scholar 

  43. Li Y, Koga M, Kasayama S, et al. Identification and characterization of high molecular weight forms of basic fibroblast growth factor in human pituitary adenomas. J Clin Endocrinol Metab. 1992;75:1436–41.

    Article  PubMed  CAS  Google Scholar 

  44. Ezzat S, Smyth HS, Ramyar L, Asa SL. Heterogenous in vivo and in vitro expression of basic fibroblast growth factor by human pituitary adenomas. J Clin Endocrinol Metab. 1995;80:878–84.

    Article  PubMed  CAS  Google Scholar 

  45. Shah PP, Fong MY, Kakar SS. PTTG induces EMT through integrin αVβ3-focal adhesion kinase signaling in lung cancer cells. Oncogene. 2012;31:3124–35.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by the Beijing Talent Program (China) no. 2060306.

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Authors and Affiliations

  1. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6, Tiantan Xili, Beijing, 100050, Dongcheng District, China

    Wang Jia, Guijun Jia & Ming Ni

  2. Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, China

    Runchun Lu

  3. Capital Medical University, Beijing, 100069, China

    Zhiqing Xu

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Correspondence to Wang Jia.

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Jia, W., Lu, R., Jia, G. et al. Expression of pituitary tumor transforming gene (PTTG) in human pituitary macroadenomas. Tumor Biol. 34, 1559–1567 (2013). https://doi.org/10.1007/s13277-013-0686-2

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  • DOI: https://doi.org/10.1007/s13277-013-0686-2

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