eRF3a/GSPT1 12-GGC allele increases the susceptibility for breast cancer development.
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 an 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.
Escola Superior de Tecnologia da Saúde de Lisboa, 1990-096 Lisboa, Portugal.
Joana
J
Malta-Vacas
Celine
C
Chauvin
Lucilia
L
Gonçalves
Antonia
A
Nazaré
Carlos
C
Carvalho
Carolino
C
Monteiro
Denyse
D
Bagrel
Olivier
O
Jean-Jean
Miguel
M
Brito
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016017:Odds Ratio; D010454:Peptide Termination Factors / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011379:Prognosis; D034622:RNA Interference; D018570:Risk Assessment; D012307:Risk Factors; D014162:Transfection
D010454:Peptide Termination Factors; C087971:peptide-chain-release factor 3