UBE2C is overexpressed in ESCC tissues and its abrogation attenuates the malignant phenotype of ESCC cell lines
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Antonio Palumbo Jr.1,2, Nathalia Meireles Da Costa1, Marco De Martino3, Romina Sepe3, Simona Pellecchia3, Vanessa Paiva Leite de Sousa1, Pedro Nicolau Neto1, Cleber Dario Kruel4, Anke Bergman1, Luiz Eurico Nasciutti2, Alfredo Fusco1,3, Luis Felipe Ribeiro Pinto1
1Programa de Carcinogênese Molecular, Instituto Nacional de Câncer - INCA, Rio de Janeiro, Brazil
2Laboratório de Interações Celulares, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro Prédio de Ciências da Saúde - Cidade Universitária, Ilha do Fundão, Rio de Janeiro, Brasil
3Istituto di Endocrinologia e Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli “Federico II”, Naples, Italy
4Departamento de Cirurgia, Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
Luis Felipe Ribeiro Pinto, email: [email protected]
Alfredo Fusco, email: [email protected]
Keywords: esophageal squamous cell carcinoma, UBE2C, diagnostic biomarker, cyclin B1, cell cycle
Received: May 15, 2016 Accepted: August 13, 2016 Published: August 29, 2016
The esophageal squamous cell carcinoma (ESCC) is widely known as a highly lethal and poor understood cancer, then requiring the search for novel molecular markers to improve its management and patients survival. Recently, ubiquitin-conjugating enzyme E2C (UBE2C) has been figuring as a prominent tumor biomarker candidate, once it has been recognized as a key player in cell cycle progression. In this way, the aim of this study was to evaluate the expression profile of UBE2C gene and protein in ESCC samples, as well as its diagnostic and prognostic marker potential, and its contribution to ESSC genesis and/or progression by performing in vitro functional assays. The analysis of UBE2C gene expression in 52 paired ESCC samples (tumor and respective histologically normal surrounding tissue), by qRT-PCR, revealed that this gene is overexpressed in 73% of ESCC samples. Subsequently, immunohistochemical analysis confirmed that UBE2C protein expression was upregulated in all ESCC cases, but absent in the histologically normal tumor surrounding tissues. Moreover, we showed that UBE2C mRNA expression was able to accurately discriminate ESCC tissue from both healthy esophageal and histologically normal tumor surrounding tissues, pointing out its role as a diagnostic marker for this cancer. Finally, we report that UBE2C affects proliferation rates and cell cycle profile of ESCC cell lines, by directly interfering with cyclin B1 protein levels, suggesting its involvement in crucial steps of ESCC carcinogenesis.
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