Universidade de Lisboa Repositório da Universidade de Lisboa

Repositório da Universidade de Lisboa >
Faculdade de Ciências (FC) >
FC - Teses de Doutoramento >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10451/1648

Título: Influence of ERF3A/GSPT1 gene expression on susceptibility to carcinogenesis
Autor: Vacas, Joana Malta, 1977-
Orientador: Brito, Rui Miguel Duque de, 1969-
Coelho, Maria Manuela, 1954-
Palavras-chave: Cancro
Expansão GGC
Expressão genética
Biologia molecular
Teses de doutoramento - 2009
Issue Date: 2009
Resumo: The eukaryotic release factor 3 (eRF3) associates with eRF1 in a complex that mediatestranslation termination. In addition to its roles in translation, eRF3 is also involved in cell cycleregulation, apoptosis and cytoskeleton assemble. Human eRF3 has two distinct isoforms, eRF3aand eRF3b, encoded by eRF3a/GSPT1 and eRF3b/GSPT2 genes.eRF3a/GSPT1 contains a stable (GGC)n expansion coding for proteins with different N-terminalextremities. We identified five alleles encoding 7, 9, 10, 11 and 12 GGC repeats in thePortuguese population, being the 10GGC allele the most frequent (F= 68.5% in the controlpopulation). The longer allele (12GGC) was exclusively detected in 5.1% of the cancer patients(N=411) with an allele frequency of 3%, corresponding to a 12-fold increased cancer risk.Our results show that the mRNA levels of eRF3a/GSPT1 are overexpressed in a significantproportion of different types of cancer. Moreover, the transcript levels of eRF3a/GSPT1 showvariation between alleles, being the 12GGC allele significantly overexpressed (p<0.001). Thelevels of eRF3a/GSPT1 transcription are not associated with eRF3a/GSPT1 amplification neitherwith the methylation pattern of the GGC expansion region.Using an in vivo assay for readthrough efficiency, we do not detect any difference in the activityof the eRF3a proteins encoded by the five different eRF3a/GSPT1 alleles. Also, no differences inthe levels of apoptosis and proliferation rates were found between cells lines. Finally, using acytokinesis-block micronucleos assay, we show that cells with the longer alleles have higherfrequencies of MN, which is probably a result of defects in mitotic spindle formation.Although the connection between eRF3a/GSPT1 and tumorigenesis is not completely elucidated,our data suggests that the presence of the 12GGC allele provides a novel risk marker for cancer.Taken together, our results show that eRF3a should be considered as a potential proto-oncogene
Descrição: Tese de doutoramento, Biologia (Biologia Molecular), Universidade de Lisboa, Faculdade de Ciências, 2009
URI: http://catalogo.ul.pt/F/?func=item-global&doc_library=ULB01&type=03&doc_number=000569463
Appears in Collections:FC - Teses de Doutoramento

Files in This Item:

File Description SizeFormat
20552_ulsd_re517_TD_Joana_Vacas_1.pdf5,42 MBAdobe PDFView/Open

Please give feedback about this item
FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpace
Formato BibTex MendeleyEndnote Logotipo do DeGóis 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.


  © Universidade de Lisboa / SIBUL
Alameda da Universidade | Cidade Universitária | 1649-004 Lisboa | Portugal
Tel. +351 217967624 | Fax +351 217933624 | repositorio@reitoria.ul.pt - Feedback - Statistics
Promotores do RCAAP   Financiadores do RCAAP

Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência PO Sociedade do Conhecimento (POSC) Portal oficial da União Europeia