Abstract. Gastric cancer is one of the most common malignancies worldwide and the second most common cause of cancer-related mortality. Previous studies revealed several genetic alterations specific to gastric cancer. In this study, we aimed to investigate the diagnostic and prognostic significance of the expression levels of the glypican 5 and glypican 6 genes (GPC5 and GPC6, respectively) in gastric cancer. For this purpose, GPC5 and GPC6 expression was quantitatively determined by quantitative polymerase chain reaction method in normal gastric mucosa and intestinal type gastric adenocarcinoma samples from 35 patients. The expression levels of GPC5 and GPC6 were compared between normal and tumor tissues. Additionally, the association of the expression levels in tumor tissues with several clinicopathological parameters was evaluated. Although GPC5 was not expressed in any of the samples, the expression of GPC6, which was detected in both groups, was found to be significantly higher in tumor tissues compared to that in normal samples (P=0.039). However, there was no statistically significant association between GPC6 expression and any of the clinicopathological parameters investigated (P>0.05). Our findings suggested that an increase in GPC6 expression levels may be implicated in gastric cancer development, but not in cancer progression.

Mediator is a large and evolutionarily conserved coactivator complex essential for RNA polymerase II (Pol II)-mediated gene regulation at multiple steps of the transcription process, including preinitiation complex (PIC) assembly and function. Here, we used the MultiBac baculovirus expression system to generate recombinant human core Mediator subcomplexes and subsequent biochemical approaches to dissect the mechanism by which Mediator facilitates direct recruitment of Pol II to core promoters. Our results highlight a pivotal role in this process for the N-terminal half (NTD) of the MED14 subunit. We show that a reconstituted 15-subunit human core Mediator complex that contains only the MED14-NTD is fully functional in facilitating both basal and activated (p53) transcription. This complex directly interacts with the C-terminal domain (CTD) of the RPB1 subunit of Pol II (RPB1 CTD) and is required for recruiting Pol II to core promoters. Moreover, recombinant RPB1 can completely reverse the human core Mediator-Pol II interaction. Notably, the human MED14-NTD region has secondary structure conservation with Schizosaccharomyces pombe. In addition, reanalysis of published cryo-EM structures of yeast Mediator-Pol II complexes strongly supports our conclusion. Thus, our analyses provide critical new insights into how Mediator binds to Pol II and recruits it to the promoters to facilitate transcription.