Use este identificador para citar ou linkar para este item: http://repositorio.bc.ufg.br/handle/ri/18062
Tipo do documento: Artigo
Título: RKIP inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy
Autor: Martinho, Olga Catarina Lopes
Pinto, Filipe Miranda Cunha
Granja, Sara
Gonçalves, Vera Miranda
Moreira, Marise Amaral Rebouças
Ribeiro, Luiz Fernando Jubé
Loreto, Celso di
Rosner, Marsha Rich
Longatto Filho, Adhemar
Abstract: Cervical cancer is one of the most common cancers in women worldwide, being high-risk group the HPV infected, the leading etiological factor. The raf kinase inhibitory protein (RKIP) has been associated with tumor progression and metastasis in several human neoplasms, however its role on cervical cancer is unclear. In the present study, 259 uterine cervix tissues, including cervicitis, cervical intraepithelial lesions and carcinomas, were analyzed for RKIP expression by immunohistochemistry. We found that RKIP expression was significantly decreased during malignant progression, being highly expressed in non-neoplastic tissues (54% of the samples; 73/135), and expressed at low levels in the cervix invasive carcinomas (,15% (19/124). Following in vitro downregulation of RKIP, we observed a viability and proliferative advantage of RKIP-inhibited cells over time, which was associated with an altered cell cycle distribution and higher colony number in a colony formation assay. An in vitro wound healing assay showed that RKIP abrogation is associated with increased migratory capability. RKIP downregulation was also associated with an increased vascularization of the tumors in vivo using a CAM assay. Furthermore, RKIP inhibition induced cervical cancer cells apoptotic resistance to cisplatin treatment. In conclusion, we described that RKIP protein is significantly depleted during the malignant progression of cervical tumors. Despite the lack of association with patient clinical outcome, we demonstrate, in vitro and in vivo, that loss of RKIP expression can be one of the factors that are behind the aggressiveness, malignant progression and chemotherapy resistance of cervical cancer.
País: Brasil
Unidade acadêmica: Faculdade de Medicina - FM (RG)
Citação: MARTINHO, Olga et al. RKIP inhibition in cervical cancer is associated with higher tumor aggressive behavior and resistance to cisplatin therapy. Plos One, California, v. 8, n. 3, p. e59104, 2013.  
Tipo de acesso: Acesso Aberto
Identificador do documento: 10.1371/journal.pone.0059104
Identificador do documento: 10.1371/journal.pone.0059104
URI: http://repositorio.bc.ufg.br/handle/ri/18062
Data de publicação: 2013
Aparece nas coleções:FM - Artigos publicados em periódicos

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