Survivin, Possible Marker and Prognostic Factor in Oral Squamous Cell Carcinomas
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Survivin is a member of the inhibitors of apoptosis (IAP) family that have been known to inhibit activated caspases in apoptosis. In contrast to most IAP family members, survivin mRNA is expressed during fetal development, is not found in normal adult tissues and is overexpressed again in the cancer. Though survivin expression has been documented in most human cancers, little is known about its expression in OSCC and its potential value as a predictor of cancer survival. The purpose of this study was to investigate survivin expression in OSCC and to evaluate its value as a prognostic marker. We evaluated survivin expressions in cancer lines and OSCC samples and investigated the relationships between survivin expressions and clinico- pathological parameters including stage, differentiation, proliferation, lymph node metastasis, blood vessel density, and gelatinolytic activity. With immunohistochemistry, we analyzed survivin expression in 38 OSCCs. Patients’clinico-pathological parameters and their survival rate were analyzed to reveal their correlations with Survivin expressions. We cultured oral cancer cell lines and evaluated the correlation between gelatinolytic activities and survivin expressions of them. Survivin protein was observed both in nuclei and cytoplasm of tumor specimens while little or not observed in normal gingival mucosal tissues. Additionally, survivin expressions were correlated with lymph node metastasis, tumor proliferation and survival rate. Survivin expression was observed in 100% of 38 samples of OSCC and its expression levels are statistically associated with the proliferative activity of the tumors, lymph node metastasis and the survival of the patients. Based on these results, survivin is commonly expressed in OSCC and may thus provide valuable prognostic information related with lymph node metastasis, proliferation and survival rate as well as a potential therapeutic target in OSCC.
Abstract
Survivin is a member of the inhibitors of apoptosis (IAP) family that have been known to inhibit activated caspases in apoptosis. In contrast to most IAP family members, survivin mRNA is expressed during fetal development, is not found in normal adult tissues and is overexpressed again in the cancer. Though survivin expression has been documented in most human cancers, little is known about its expression in OSCC and its potential value as a predictor of cancer survival. The purpose of this study was to investigate survivin expression in OSCC and to evaluate its value as a prognostic marker. We evaluated survivin expressions in cancer lines and OSCC samples and investigated the relationships between survivin expressions and clinico- pathological parameters including stage, differentiation, proliferation, lymph node metastasis, blood vessel density, and gelatinolytic activity. With immunohistochemistry, we analyzed survivin expression in 38 OSCCs. Patients’clinico-pathological parameters and their survival rate were analyzed to reveal their correlations with Survivin expressions. We cultured oral cancer cell lines and evaluated the correlation between gelatinolytic activities and survivin expressions of them. Survivin protein was observed both in nuclei and cytoplasm of tumor specimens while little or not observed in normal gingival mucosal tissues. Additionally, survivin expressions were correlated with lymph node metastasis, tumor proliferation and survival rate. Survivin expression was observed in 100% of 38 samples of OSCC and its expression levels are statistically associated with the proliferative activity of the tumors, lymph node metastasis and the survival of the patients. Based on these results, survivin is commonly expressed in OSCC and may thus provide valuable prognostic information related with lymph node metastasis, proliferation and survival rate as well as a potential therapeutic target in OSCC.
참고문헌 (49)
- Pisani P, "Estimates of the worldwide mortality from 25 cancers in 1990", Int J Cancer, 83, pp.18~29 (1990)
- Schliephake H, "Prognostic relevance of molecular markers of oral cancer - a review", Int J Oral Maxillofac Surg, 32, pp.233~245 (2003)
- Friedlander PL, "The use of genetic markers in the clinical care of patients with head and neck cancer", Arch Otolaryngol Head Neck Surg, 129, pp.363~366 (2003)
- Reed JC, "The survivin saga goes in vivo", J Clin Invest, 108, pp.965~969 (2001)
- Ambrosini G, "Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting", J Biol Chem, 273, pp.461~466 (1998)
- LaCasse E, "The inhibitor of apoptosis (IAPs) and their emerging role in cancer", Oncogene, 17, pp.3247~3259 (1998)
- Deveraux QK, "IAP family proteins - suppressors of apoptosis", Genes Dev, 13, pp.239~252 (1999)
- Shin S, "An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and ?7", Biochemistry, 40, pp.1117~1123 (2001)
- O’Connor DS, "Regulation of apoptosis at cell division by p34cdc2 phosphorylation of surviving", Proc Natl Acad Sci USA, 97, pp.13103~13107 (2000)
- Swana HS, "Tumor content of the antiapoptosis molecule survivin and recurrence of bladder cancer", N Engl J Med, 341, pp.452~453 (1999)
- Adida C, "Prognostic significance of survivin expression in diffuse large B-cell lymphomas", Blood, 96, pp.1921~1925 (2000)
- Kawasaki H, "Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer", Cancer Res, 58, pp.5071~5074 (1998)
- Ito T, "Survivin promotes cell proliferation in human hepatocellular carcinoma", Hepatology, 31, pp.1080~1085 (2000)
- Nakagawara A, "Molecular basis of spontaneous regression of neuroblastoma: role of neurotrophic signals and genetic abnormalities", Hum Cell, 11, pp.115~124 (1998)
- Monzo M, "A novel antiapoptosis gene: reexpression of survivin messenger RNA as a prognosis marker in nonsmall-cell lung cancers", J Clin Oncol, 17, pp.2100~2104 (1999)
- Satoh K, "Expression of survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct cell tumors", Cancer, 92, pp.271~278 (2001)
- Xing N, "Neuroendocrine cells in human prostate over-express the anti-apoptosis protein surviving", Prostate, 48, pp.7~15 (2001)
- Takamizawa S, "The survivin : fas ratio in pediatric renal tumors", J Pediatr Surg, 36, pp.37~42 (2001)
- Okada E, "Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients", Cancer Lett, 163, pp.109~116 (2001)
- Noguchi N, "Effects of fibroblast growth inhibitor on proliferation and metastasis of oral squamous cell carcinoma", Oral Oncol, 39, pp.240~247 (2003)
- Bosari S, "Microvessel quantitation and prognosis in invasive breast carcinoma", Hum Pathol, 23, pp.755~761 (1992)
- Kennedy SM, "Prognostic importance of survivin in breast cancer", Br J Cancer, 88, pp.1077~1083 (2003)
- Hong SD, "Expression of matrix metalloproteinase-2 and -9 in oral squamous cell carcinomas with regard to the metastatic potential", Oral Oncol, 36, pp.207~213 (2000)
- Myoung H, "Anti-cancer effect of genistein in oral squamous cell carcinoma with respect to angiogenesis and in vitro invasion", Cancer Sci, 94, pp.215~220 (2003)
- Ambrosini G, "A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma", Nat Med, 3, pp.917~921 (1997)
- Muzio LL, "Expression of the Apoptosis Inhibitor survivin in Aggressive Squamous Cell Carcinoma", Experimental and Molecular Pathology, 70, pp.249~254 (2001)
- Miyachi K, "Correlation between survivin mRNA expression and lymph node metastasis in gastric cancer", Gastric Cancer, 6, pp.217~224 (2003)
- O’Driscoll L, "Glynn S: Lack of prognostic significance of survivin, survivin-deltaEx3, survivin-2B, galectin-3, bag-1, bax-alpha and MRP-1 mRNAs in breast cancer", Cancer Lett, 201, pp.225~236 (2003)
- Adida C, "Expression and prognostic significance of survivin in de novo acute myeloid leukaemia", Br J Haematol, 111, pp.196~203 (2000)
- Frost M, "Immunohistochemical localization of survivin in benign cervical mucosa, cervical dysplasia, and invasive squamous cell carcinoma", Am J Clin Pathol, 117, pp.738~744 (2002)
- Rodriguez JA, "CRM1-mediated nuclear export determines the cytoplasmic localization of the antiapoptotic protein surviving", Exp Cell Res, 275, pp.44~53 (2002)
- Konno R, "Expression of survivin and Bcl-2 in the normal human endometrium", Mol Hum Report, 6, pp.529~534 (2000)
- Li F, "Anti-apoptosis gene, survivin, and prognosis, Control of apoptosis and mitotic spindle checkpoint by surviving", Nature, 396, pp.580~584 (1998)
- Uren AG, "Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype", Curr Biol, 10, pp.1319~1328 (2000)
- Altieri DC, "The molecular basis and potential role of survivin in cancer diagnosis and therapy", Trends Mol Med, 7, pp.542~547 (2001)
- Hedley DW, "Method for analysis of cellular DNA content of paraffin-embedded pathological material using flowcytometry", J Histochem Cytochem, 31, pp.1333~1335 (1983)
- Grossman D, "Inhibition of melanoma tumor growth in vivo by survivin targeting", Proc Natl Acad Sci USA, 98, pp.635~640 (2001)
- Suzuki A, "Survivin initiates cell cycle entry by the competitive interaction with Cdk4", p16(INK4a) and Cdk2, Oncogene, pp.2000, 19[DOI]
- Adida C, "Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation", Am J Pathol, 152, pp.43~49 (1998)
- Liotta LA, "Tumor invasion and the extracellular matrix", Lab Invest, 49, pp.636~649 (1983)
- Wyllie AH, "Apoptosis and carcinogenesis", Br J Cancer, 80, pp.34~37 (1999)
- Sierra A, "Bcl-2 with loss of apoptosis allows accumulation of genetic alterations: a pathway to metastatic progression in human breast cancer", Int J Cancer, 89, pp.142~147 (2000)
- Glinsky GV, "Apoptosis and metastasis: a superior resistance of metastatic cancer cells to programmed cell death", Cancer Lett, 101, pp.43~51 (1996)
- Glinsky GV, "Apoptosis and metastasis: increased apoptosis resistance of metastatic cancer cells is associated with the profound deficiency of apoptosis execution mechanisms", Cancer Lett, 115, pp.185~193 (1997)
- Kato J, "Expression of survivin in esophageal cancer: correlation with the prognosis and response to chemotherapy", Int J Cancer, 95, pp.92~95 (2001)
- Yoshida H, "Survivin, bcl-2 and matrix metalloproteinase-2 enhance progression of clear cell- and serous-type ovarian carcinomas", Int J Oncol, 19, pp.537~542 (2001)
- Xiangming C, "Angiogenesis as an unfavorable factor related to lymph node metastasis in early gastric cancer", Ann Surg Oncol, 5, pp.585~589 (1998)
- Maeda K, "Prognostic value of vascular endothelial growth factor expression in gastric carcinoma", Cancer, 77, pp.858~863 (1996)
- Tran J, "Marked induction of the IAP family antiapoptotic proteins survivin and XIAP by VEGF in vascular endothelial cells", Biochem Biophys Res Commun, 264, pp.781~788 (1999)
