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.

O auteur a ver-se a si mesmo ao espelho: as alegorias do enunciador em Jean Cocteau

ABSTRACT - Jean Cocteau, French cinema auteur avant la lettre, has consecrated his uniqueness to the defense of the “poet” and the promotion of its artistic ideals, before the French Nouvelle Vague inspired the break away from the filmic tradition and ahead of the eulogistic tendency to consider the director the undisputed creative entity of the filmmaking process. The Orphic trilogy expresses Cocteau’s cinematic philosophy in action. In other words, it reveals the way by which the creative entity affirms itself as the major filmic enunciator, through an allegorical relationship with vision. Therefore, Cocteau’s self-reflexive metacinema conjoins, in a fertile attunement, the starting point and the ultimate goal, the creation and the reception. Without being exactly a cinema about the cinema, this artistic practice is, nonetheless, very much with the cinema, feeding as it does on its essence. The films Le Sang d’un poète (“The Blood of a Poet”, 1932), Orphée (“Orpheus”, 1950) and Le Testament d’Orphée, ou ne me demandez pas pourquoi! (“Testament of Orpheus”, 1960) recreate, in allegorical form, the double creative function: the look of the directing entity reflects the gaze of the observer, just as this one always restores the presence of the creator. In short: Cocteau’s films, more than anyone else’s, deliberately reflect its auteur as enunciator.