Orientador(es)
Resumo(s)
It is now widely recognized that translation factors are involved in cancer development and that components of the translation machinery that are deregulated in cancer cells may become targets for cancer therapy. The eukaryotic Release Factor 3 (eRF3) is a GTPase that associates with eRF1 in a complex that mediates translation termination. eRF3a/GSPT1 first exon contains a (GGC)n expansion coding for proteins with different N-terminal extremities. Herein we show that the longer allele (12-GGC) is present in 5.1% (7/137) of the breast cancer patients analysed and is absent in the control population (0/135), corresponding to all increased risk for cancer development, as revealed by Odds Ratio analysis. mRNA quantification suggests that patients with the 12-GGC allele overexpress eRF3a/GSPT1 in tumor tissues relative to the normal adjacent tissues. However, using an in vivo assay for translation termination in HEK293 cells, we do not detect any difference in the activity of the eRF3a proteins encoded by the various eRF3a/GSPT1 alleles. Although the connection between the presence of eRF3a/GSPT1 12-GGC allele and tumorigenesis is still unknown, our data suggest that the presence of the 12-GGC allele provides a potential novel risk marker for various types of cancer.. - Ministerio da Ciencia e Ensino Superior [PTDC/SAU-GMG/67031/2006, SFRH/BD/21468/2005]; Association pour la Recherche sur le Cancer [4891]. - The authors thank to Dr Raul Lobato-Faria from Hospital Fernando da Fonseca for clinical data compilation. This work was supported by Fundacao para a Ciencia e Tecnologia from Ministerio da Ciencia e Ensino Superior (project PTDC/SAU-GMG/67031/2006 and grant SFRH/BD/21468/2005 to J.M.V.) and by the Association pour la Recherche sur le Cancer (grant 4891 to O.J.J.).
Descrição
Palavras-chave
Oncology
Contexto Educativo
Citação
ONCOLOGY REPORTS. - Vol. 21, n. 6 (JUN 2009), p. 1551-1558
Editora
PROFESSOR D A SPANDIDOS