Abstract:The purpose of this study was to investigate the expression of pituitary tumor transforming gene (PTTG) and basic fibroblast growth factor (bFGF) in oral squamous cell carcinoma (OSCC) and tongue cancer cell line Tca8113, as well as their effects on each other. We detected PTTG protein and bFGF in OSCC tissues from 56 cases using the streptavidin-biotin peroxidase (S-P) method; additionally, after being treated with different concentrations of anti bFGF or PTTG antibody, PTTG or bFGF expression in Tca8113 was examined by immunocytochemistry. The results were as follows: (1) Positive rates of PTTG protein and bFGF were 78.2% and 67.3% in OSCC, respectively, which were significantly higher than those in normal mucosal tissues (P<0.05). PTTG protein was significantly up-regulated in poorly and moderately differentiated tumors compared to well differentiated tumors (P<0.05), and there was also a significant difference between tumors with lymph node metastasis and tumors without lymph node metastasis (P<0.05). PTTG protein expression was positively correlated with bFGF (r = 0.382, P<0.05); (2) PTTG protein emitted strong fluorescence in Tca8113, and it decreased after being treated with anti-bFGF antibody. Anti-PTTG antibody also had an inhibitive effect on bFGF expression. In summary, the overexpression of PTTG protein is closely related with OSCC differentiation and lymph node metastasis. PTTG protein expression conforms to bFGF in OSCC tissues and Tca8113 cells. Detection of both PTTG and bFGF may help to judge the degree of malignancy and prognosis of patients with OSCC.
Yamazaki Y, Chiba I, Hirai A, Satoh C, Sakakibara N, Notani K, Iizuka T, Totsuka Y. Clinical value of geneticallydiagnosed lymph node micrometastasis for patients with oral squamouscell carcinoma. Head Neck, 2005, 27(8): 676―681 doi: 10.1002/hed.20200
Eckert A W, Lautner M H, Dempf R, Schubert J, Bilkenroth U. Prognostic factors for oralsquamous cell carcinoma. Chirurg, 2009, 80(2): 138―143 doi: 10.1007/s00104-008-1647-y
Arduino P G, Carrozzo M, Chiecchio A, Broccoletti R, Tirone F, Borra E, Bertolusso G, Gandolfo S. Clinical and histopathologicindependent prognostic factors in oral squamous cell carcinoma: aretrospective study of 334 cases. J OralMaxillofac Surg, 2008, 66(8): 1570―1579 doi: 10.1016/j.joms.2007.12.024
Zhang X, Horwitz G A, Prezant T R, Valentini A, Nakashima M, Bronstein MD, Melmed S. Structure,expression, and function of human pituitary tumor transforming gene(PTTG). J Mol Endocrinol, 1999, 13(1): 156―166 doi: 10.1210/me.13.1.156
Saez C, Japon M A, Ramos Morales F, Romero F, Sequra D I, Tortolero M, Pintor Toro J A. hPTTG is over expressed in pituitary adenomas and other primary epithelialneoplasias. Oncogene, 1999, 18(39): 5473―5476 doi: 10.1038/sj.onc.1202914
Zhou C, Liu S, Zhou X, Xue L, Quan L, Lu N, Zhang G, Bai J, Wang Y, Liu Z, Zhan Q, Zhu H, Xu N. Overexpression of human pituitary tumor transforminggene (hPTTG), is regulated by beta-catenin/TCF pathway in human esophagealsquamous cell carcinoma. Int J Cancer, 2005, 113(6): 891―898 doi: 10.1002/ijc.20642
Kim D, Pemberton H, Stratford A L, Buelaert K, Watkinson J C, Lopes V, Franklyn J A, McCabe C J. Pituitary tumour transforminggene (PTTG) induces genetic instability in thyroid cells. Oncogene, 2005, 24(30): 4861―4866 doi: 10.1038/sj.onc.1208659
Li C, Shintani S, Terakado N, Klosek S K, Ishikawa T, Nakashiro K, Hamakawa H. Microvesseldensity and expression of vascular endothelial growth factor, basicfibroblast growth factor, and platelet-derived endothelial growthfactor in oral squamous cell carcinomas. Int J Oral Maxillofac Surg, 2005, 34(5): 559―565 doi: 10.1016/j.ijom.2004.10.016
Zhao Z S, Wang Y Y, Ye Z Y, Tao H Q. Prognosticvalue of tumor-related molecular expression in gastric carcinoma. Pathol Oncol Res, 2009, Mar 18, Epub ahead of print doi: 10.1007/s12253-009-9158-9
Ali M A. Lymphatic microvessel density and the expression of lymphangiogenicfactors in oral squamous cell carcinoma. Med Princ Pract, 2008, 17(6): 486―492 doi: 10.1159/000151572
Tsai S J, Lin S J, Cheng Y M, Chen H M, Wing L Y. Expression and functional analysis ofpituitary tumor transforming gene-1 in uterine leiomyomas. J Clin Endocrinol Metab, 2005, 90(6): 3715―3723 doi: 10.1210/jc.2004-2303
Panguluri S K, Yeakel C, Kakar S S. PTTG: an important target gene for ovarian cancer therapy. J Ovarian Res, 2008, 1(1): 6 doi: 10.1186/1757-2215-1-6
Solbach C, Roller M, Eckerdt F, Peters S, Knecht R. Pituitary tumor- transforminggene expression is a prognostic marker for tumor recurrence in squamouscell carcinoma of the head and neck. BMCCancer, 2006, 6: 242 doi: 10.1186/1471-2407-6-242
Kakar S S, Malik M T. Suppression of lung cancerwith siRNA targeting PTTG. Int J Oncol, 2006, 29(2): 387―395
Zhao E, Xu J, Yin X, Sun Y, Shi J, Li X. Detectionof deregulated pathways to lymphatic metastasis in oral squamous cellcarcinoma. Pathol Oncol Res, 2009, Feb 12, Epub ahead of print
Chikazawa M, Inoue K, Fukata S, Karashima T, Shuin T. Expression of angiogenesis-relatedgenes regulates different steps in the process of tumor growth andmetastasis in human urothelial cell carcinoma of the urinary bladder. Pathobiology, 2008, 75(6): 335―345 doi: 10.1159/000164218
Ali M A. Lymphatic microvessel density and the expression of lymphangiogenicfactors in oral squamous cell carcinoma. Med Princ Pract, 2008, 17(6): 486―492 doi: 10.1159/000151572
Johannsdottir H K, Jonsson G, Johannesdottir G, Agnarsson B A, Eerola H, Arason A, Eqilsson V. Chromosome5 imbalance mapping in breast tumors from BRCA1 and BRCA2 mutationcarriers and sporadic breast tumors. IntJ Cancer, 2006, 119(5): 1052―1060 doi: 10.1002/ijc.21934
Hamid T, Kakar S S. PTTG and cancer. Histo Histopathol, 2003, 18(1): 245―251
Chesnokova V, Zonis S, Kovacs K, Ben-Shlomo A, Wawrowsky K, Bannykh S, Melmed S. p21(Cip1)restrains pituitary tumor growth.. ProcNatl Acad Sci USA, 2008, 105(45): 17498―17503 doi: 10.1073/pnas.0804810105
De Luca A, Carotenuto A, Rachiglio A, Gallo M, Maiello M R, Aldinucci D, Pinto A, Normanno N. The role of the EGFR signaling in tumor microenvironment. J Cell Physiol, 2008, 214(3): 559―567 doi: 10.1002/jcp.21260