E-cadherin and its transcriptional repressor Snail1 (Snai1) are two factors that control epithelial phenotype. Expression of Snail1 promotes the conversion of epithelial cells to mesenchymal cells, and occurs concomitantly with the downregulation of E-cadherin and the upregulation of expression of mesenchymal genes such as those encoding fibronectin and LEF1. We studied the molecular mechanism controlling the expression of these genes in mesenchymal cells. Forced expression of E-cadherin strongly downregulated fibronectin and LEF1 RNA levels, indicating that E-cadherin-sensitive factors are involved in the transcription of these genes. E-cadherin overexpression decreased the transcriptional activity of the fibronectin promoter and reduced the interaction of β-catenin and NF-κB with this promoter. Similar to β-catenin, NF-κB was found, by co-immunoprecipitation and pull-down assays, to be associated with E-cadherin and other cell-adhesion components. Interaction of the NF-κB p65 subunit with E-cadherin or β-catenin was reduced when adherens junctions were disrupted by K-ras overexpression or by E-cadherin depletion using siRNA. These conditions did not affect the association of p65 with the NF-κB inhibitor IκBα. The functional significance of these results was stressed by the stimulation of NF-κB transcriptional activity, both basal and TNF-α-stimulated, induced by an E-cadherin siRNA. Therefore, these results demonstrate that E-cadherin not only controls the transcriptional activity of β-catenin but also that of NF-κB. They indicate too that binding of this latter factor to the adherens junctional complex prevents the transcription of mesenchymal genes.

ObjectiveTo estimate the prevalence of HIV testing among patients diagnosed with an indicator condition (IC) for HIV, seen in primary care (PC) in Catalonia, and to estimate the prevalence of HIV infection among those patients.DesignCross-sectional and population-based study in patients aged between 16 and 65 diagnosed with an IC within PC in Catalonia.MethodsData used in this study were extracted from a large population-based public health database in Spain, the Information System for the Development of Research in Primary Care (SIDIAP). All participants registered in SIDIAP from 1 January 2010 to 31 August 2012 and with a diagnosis of an IC were screened to identify those with an HIV test within the following 4 months.Results99 426 patients were diagnosed with an IC during the study period. In these patients, there were 102 647 episodes in which at least one IC was diagnosed. An HIV test was performed within 4 months in only 18 515 of the episodes in which an IC was diagnosed (18.5%). The prevalence of HIV infection was 1.46%. Women (OR 1.35, 95% CI 1.30 to 1.39), people aged 50 or over (OR 2.85, 95% CI 2.69 to 3.00) and patients having a single IC (OR 3.59. 95% CI 3.20 to 4.03) had the greatest odds of not having an HIV test.ConclusionsThe study highlights the persistence of missed opportunities for HIV testing within PC in Catalonia. Urgent engagement with PC professionals is required in order to increase HIV testing and prevent late HIV diagnoses.

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