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Journal of Cancer Research and Clinical Oncology
Published in: Journal of Cancer Research and Clinical Oncology 1/2009

01-01-2009 | Original Paper

Survivin gene-expression and splicing isoforms in oral squamous cell carcinoma

Authors: Salvatore De Maria, Giuseppe Pannone, Pantaleo Bufo, Angela Santoro, Rosario Serpico, Salvatore Metafora, Corrado Rubini, Daniela Pasquali, Silvana M. Papagerakis, Stefania Staibano, Gaetano De Rosa, Ernesto Farina, Monica Emanuelli, Andrea Santarelli, Maria Ada Mariggiò, Lucio Lo Russo, Lorenzo Lo Muzio

Published in: Journal of Cancer Research and Clinical Oncology | Issue 1/2009

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Abstract

Purpose

Survivin, an inhibitor of apoptosis protein and a cell cycle regulator, has been detected in the majority of human cancers. Five splice variants (survivin, survivin-2α, survivin-2B, survivin-3B, and survivin-ΔEx3) have been identified; their expressions have been investigated here.

Methods

By means of RT real-time PCR and immunohistochemistry, we have evaluated survivin isoform expressions at both mRNA and protein levels in human normal oral tissue, precancerous lesions, and oral squamous cell carcinoma (OSCC). Their correlations with the pathological findings have also been analyzed.

Results

Expression levels of all survivin transcript variants were markedly elevated in OSCC when compared to normal tissues. One-way analysis of variance (ANOVA) revealed highly significant up-regulation of survivin (P = 0.001), survivin-ΔEx3 (P = 0.001) and survivin-2B (P = 0.004), whereas survivin-3B showed a minor increase in OSCC compared to normal mucosa.

Conclusions

Our findings suggest that survivin isoforms deregulation may have significant implications in tumor aggressiveness and prognosis.
Literature
Altura RA, Olshefski RS, Jiang Y, Boue DR (2003) Nuclear expression of survivin in paediatric ependymomas and choroid plexus tumours correlates with morphologic tumour grade. Br J Cancer 89l:1743–1749CrossRef
Ambrosini G, Adida C, Altieri DC (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3l:917–921CrossRef
Caldas H, Honsey LE, Altura RA (2005a) Survivin 2alpha: a novel survivin splice variant expressed in human malignancies. Mol Cancer 4l:11CrossRef
Caldas H, Jiang Y, Holloway MP, Fangusaro J, Mahotka C, Conway EM, Altura RA (2005b) Survivin splice variants regulate the balance between proliferation and cell death. Oncogene 24l:1994–2007CrossRef
Chawla-Sarkar M, Bae SI, Reu FJ, Jacobs BS, Lindner DJ, Borden EC (2004) Downregulation of Bcl-2, FLIP or IAPs (XIAP and survivin) by siRNAs sensitizes resistant melanoma cells to Apo2L/TRAIL-induced apoptosis. Cell Death Differ 11l:915–923CrossRef
Crnkovic-Mertens I, Semzow J, Hoppe-Seyler F, Butz K (2006) Isoform-specific silencing of the Livin gene by RNA interference defines Livin beta as key mediator of apoptosis inhibition in HeLa cells. J Mol Med 84l:232–240CrossRef
Dohi T, Okada K, Xia F, Wilford CE, Samuel T, Welsh K, Marusawa H, Zou H, Armstrong R, Matsuzawa S, Salvesen GS, Reed JC, Altieri DC (2004) An IAP–IAP complex inhibits apoptosis. J Biol Chem 279l:34087–34090CrossRef
Fangusaro JR, Jiang Y, Holloway MP, Caldas H, Singh V, Boue DR, Hayes J, Altura RA (2005) Survivin, survivin-2B, and survivin-deltaEx3 expression in medulloblastoma: biologic markers of tumour morphology and clinical outcome. Br J Cancer 92l:359–365
Fortugno P, Wall NR, Giodini A, O’Connor DS, Plescia J, Padgett KM, Tognin S, Marchisio PC, Altieri DC (2002) Survivin exists in immunochemically distinct subcellular pools and is involved in spindle microtubule function. J Cell Sci 115l:575–585
Fukuda S, Pelus LM (2001) Regulation of the inhibitor-of-apoptosis family member survivin in normal cord blood and bone marrow CD34(+) cells by hematopoietic growth factors: implication of survivin expression in normal hematopoiesis. Blood 98l:2091–2100CrossRef
Fukuda S, Mantel CR, Pelus LM (2004) Survivin regulates hematopoietic progenitor cell proliferation through p21WAF1/Cip1-dependent and -independent pathways. Blood 103l:120–127CrossRef
Grabowski P, Kuhnel T, Muhr-Wilkenshoff F, Heine B, Stein H, Hopfner M, Germer CT, Scherubl H (2003) Prognostic value of nuclear survivin expression in oesophageal squamous cell carcinoma. Br J Cancer 88l:115–119CrossRef
Grabowski P, Griss S, Arnold CN, Horsch D, Goke R, Arnold R, Heine B, Stein H, Zeitz M, Scherubl H (2005) Nuclear survivin is a powerful novel prognostic marker in gastroenteropancreatic neuroendocrine tumor disease. Neuroendocrinology 81l:1–9CrossRef
International union against cancer (2000) TNM classification of malignant tumours. Wiley, New York
Islam A, Kageyama H, Hashizume K, Kaneko Y, Nakagawara A (2000a) Role of survivin, whose gene is mapped to 17q25, in human neuroblastoma and identification of a novel dominant-negative isoform, survivin-beta/2B. Med Pediatr Oncol 35l:550–553CrossRef
Islam A, Kageyama H, Takada N, Kawamoto T, Takayasu H, Isogai E, Ohira M, Hashizume K, Kobayashi H, Kaneko Y, Nakagawara A (2000b) High expression of survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma. Oncogene 19l:617–623CrossRef
Krysan K, Merchant FH, Zhu L, Dohadwala M, Luo J, Lin Y, Heuze-Vourc’h N, Pold M, Seligson D, Chia D, Goodglick L, Wang H, Strieter R, Sharma S, Dubinett S (2004) COX-2-dependent stabilization of survivin in non-small cell lung cancer. FASEB J 18l:206–208
Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, Altieri DC (1998) Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 396l:580–584
Li CY, Chu JY, Yu JK, Huang XQ, Liu XJ, Shi L, Che YC, Xie JY (2004) Regulation of alternative splicing of Bcl-x by IL-6, GM-CSF and TPA. Cell Res 14l:473–479CrossRef
Liu T, Brouha B, Grossman D (2004) Rapid induction of mitochondrial events and caspase-independent apoptosis in survivin-targeted melanoma cells. Oncogene 23l:39–48CrossRef
Livak KJ, Schmittgen TD (2001) is of relative gene expression data using real-time quantitative PCR and the 2[-delta delta C(T)] method. Methods 25l:402–408CrossRef
Lo Muzio L, Staibano S, Pannone G, Mignogna MD, Mariggio A, Salvatore G, Chieffi P, Tramontano D, De Rosa G, Altieri DC (2001) Expression of the apoptosis inhibitor survivin in aggressive squamous cell carcinoma. Exp Mol Pathol 70l:249–254CrossRef
Lo Muzio L, Pannone G, Leonardi R, Staibano S, Mignogna MD, De Rosa G, Kudo Y, Takata T, Altieri DC (2003a) Survivin, a potential early predictor of tumor progression in the oral mucosa. J Dent Res 82l:923–928
Lo Muzio L, Pannone G, Staibano S, Mignogna MD, Rubini C, Mariggio MA, Procaccini M, Ferrari F, De Rosa G, Altieri DC (2003b) Survivin expression in oral squamous cell carcinoma. Br J Cancer 89l:2244–2248CrossRef
Lo Muzio L, Campisi G, Giovannelli L, Ammatuna P, Greco I, Staibano S, Pannone G, De Rosa G, Di Liberto C, D’Angelo M (2004) HPV DNA and survivin expression in epithelial oral carcinogenesis: a relationship? Oral Oncol 40l:736–741CrossRef
Lo Muzio L, D’Angelo M, Procaccini M, Bambini F, Calvino F, Florena AM, Franco V, Giovannelli L, Ammatuna P, Campisi G (2005a) Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: use of fuzzy neural networks. Int J Cancer 115l:717–723CrossRef
Lo Muzio L, Farina A, Rubini C, Pezzetti F, Stabellini G, Laino G, Santarelli A, Pannone G, Bufo P, de Lillo A, Carinci F (2005b) Survivin as prognostic factor in squamous cell carcinoma of the oral cavity. Cancer Lett 225l:27–33CrossRef
Lopes R, Castro I, Pontes P, Candeias J, Lemoine NR, Sambade C (2005) Expression profile of survivin in acute leukaemias: the importance of differential splicing. Leukemia 19l:1284–1286CrossRef
Lu B, Gonzalez A, Massion PP, Shyr Y, Shaktour B, Carbone DP, Hallahan DE (2004) Nuclear survivin as a biomarker for non-small-cell lung cancer. Br J Cancer 91l:537–540CrossRef
Mahotka C, Wenzel M, Springer E, Gabbert HE, Gerharz CD (1999) Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties. Cancer Res 59l:6097–6102
Mahotka C, Krieg T, Krieg A, Wenzel M, Suschek CV, Heydthausen M, Gabbert HE, Gerharz CD (2002a) Distinct in vivo expression patterns of survivin splice variants in renal cell carcinomas. Int J Cancer 100l:30–36CrossRef
Mahotka C, Liebmann J, Wenzel M, Suschek CV, Schmitt M, Gabbert HE, Gerharz CD (2002b) Differential subcellular localization of functionally divergent survivin splice variants. Cell Death Differ 9l:1334–1342CrossRef
Martinez A, Bellosillo B, Bosch F, Ferrer A, Marce S, Villamor N, Ott G, Montserrat E, Campo E, Colomer D (2004) Nuclear survivin expression in mantle cell lymphoma is associated with cell proliferation and survival. Am J Pathol 164l:501–510
Marusawa H, Matsuzawa S, Welsh K, Zou H, Armstrong R, Tamm I, Reed JC (2003) HBXIP functions as a cofactor of survivin in apoptosis suppression. Embo J 22l:2729–2740CrossRef
O’Connor DS, Schechner JS, Adida C, Mesri M, Rothermel AL, Li F, Nath AK, Pober JS, Altieri DC (2000) Control of apoptosis during angiogenesis by survivin expression in endothelial cells. Am J Pathol 156l:393–398
Okada E, Murai Y, Matsui K, Isizawa S, Cheng C, Masuda M, Takano Y (2001) Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients. Cancer Lett 163l:109–116CrossRef
Ryan B, O’Donovan N, Browne B, O’Shea C, Crown J, Hill AD, McDermott E, O’Higgins N, Duffy MJ (2005) Expression of survivin and its splice variants survivin-2B and survivin-deltaEx3 in breast cancer. Br J Cancer 92l:120–124CrossRef
Schwerk C, Schulze-Osthoff K (2005) Regulation of apoptosis by alternative pre-mRNA splicing. Mol Cell 19l:1–13CrossRef
Shin S, Sung BJ, Cho YS, Kim HJ, Ha NC, Hwang JI, Chung CW, Jung YK, Oh BH (2001) An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry 40l:1117–1123CrossRef
Shinohara ET, Gonzalez A, Massion PP, Chen H, Li M, Freyer AS, Olson SJ, Andersen JJ, Shyr Y, Carbone DP, Johnson DH, Hallahan DE, Lu B (2005) Nuclear survivin predicts recurrence and poor survival in patients with resected nonsmall cell lung carcinoma. Cancer 103l:1685–1692CrossRef
Song Z, Yao X, Wu M (2003) Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis. J Biol Chem 2781:23130–23140CrossRef
Suga K, Yamamoto T, Yamada Y, Miyatake S, Nakagawa T, Tanigawa N (2005) Correlation between transcriptional expression of survivin isoforms and clinicopathological findings in human colorectal carcinomas. Oncol Rep 13l:891–897
Taubert H, Kappler M, Bache M, Bartel F, Kohler T, Lautenschlager C, Blumke K, Wurl P, Schmidt H, Meye A, Hauptmann S (2005) Elevated expression of survivin-splice variants predicts a poor outcome for soft-tissue sarcomas patients. Oncogene 24l:5258–5261CrossRef
Tonini G, Vincenzi B, Santini D, Scarpa S, Vasaturo T, Malacrino C, Coppola R, Magistrelli P, Borzomati D, Baldi A, Antinori A, Caricato M, Nuzzo G, Picciocchi A (2005) Nuclear and cytoplasmic expression of survivin in 67 surgically resected pancreatic cancer patients. Br J Cancer 92l:2225–2232CrossRef
Uchida H, Tanaka T, Sasaki K, Kato K, Dehari H, Ito Y, Kobune M, Miyagishi M, Taira K, Tahara H, Hamada H (2004) Adenovirus-mediated transfer of siRNA against survivin induced apoptosis and attenuated tumor cell growth in vitro and in vivo. Mol Ther 10l:162–171CrossRef
Vegran F, Boidot R, Oudin C, Riedinger JM, Lizard-Nacol S (2005) Distinct expression of Survivin splice variants in breast carcinomas. Int J Oncol 27l:1151–1157
Venables JP (2004) Aberrant and alternative splicing in cancer. Cancer Res 64l:7647–7654CrossRef
Venables JP (2006) Unbalanced alternative splicing and its significance in cancer. Bioessays 28l:378–386CrossRef
Vischioni B, van der Valk P, Span SW, Kruyt FA, Rodriguez JA, Giaccone G (2004) Nuclear localization of survivin is a positive prognostic factor for survival in advanced non-small-cell lung cancer. Ann Oncol 15l:1654–1660CrossRef
Wheatley SP, McNeish IA (2005) Survivin: a protein with dual roles in mitosis and apoptosis. Int Rev Cytol 247l:35–88CrossRef
Xu Y, Fang F, Ludewig G, Jones G, Jones D (2004) A mutation found in the promoter region of the human survivin gene is correlated to overexpression of survivin in cancer cells. DNA Cell Biol 23l:527–537
Yu SW, Wang H, Poitras MF, Coombs C, Bowers WJ, Federoff HJ, Poirier GG, Dawson TM, Dawson VL (2002) Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 297l:259–263CrossRef
Zaffaroni N, Pennati M, Daidone MG (2005) Survivin as a target for new anticancer interventions. J Cell Mol Med 9l:360–372CrossRef
Metadata
Title
Survivin gene-expression and splicing isoforms in oral squamous cell carcinoma
Authors
Salvatore De Maria
Giuseppe Pannone
Pantaleo Bufo
Angela Santoro
Rosario Serpico
Salvatore Metafora
Corrado Rubini
Daniela Pasquali
Silvana M. Papagerakis
Stefania Staibano
Gaetano De Rosa
Ernesto Farina
Monica Emanuelli
Andrea Santarelli
Maria Ada Mariggiò
Lucio Lo Russo
Lorenzo Lo Muzio
Publication date
01-01-2009
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 1/2009
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-008-0433-z

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