Differential Notch1 and Notch2 expression in non-small cell lung cancer

Introduction: NOTCH signaling can be deregulated in non-small cell lung cancer and can have oncogenic or tumor suppressive functions. NOTCH1 is regulated equally with NOTCH2, and the stability of the expression of those Notch receptors could determine the biological functions of lung cancer cells. Purpose: To estimate expression level of NOTCH2 receptor in diverse NSCLC cell lines. Furthermore, we compared the mRNA level of NOTCH2 expression to the level of NOTCH1 expression. Materials and methods: We have evaluated the mRNA manifestation of NOTCH1 and NOTCH2 genes by using quantitative real time method (RT-PCR). Moreover, we associated the results from NSCLC cells with results achieved in non-cancerous human bronchial epithelial cells (HBEpC). Results: The expression level of NOTCH1 and NOTCH2 was downregulated in NSCLC cell lines, when related to HBEpC. Nevertheless, the decrease in NOTCH1 expression was significant, whereas NOTCH2 was not much different from the expression in control cells. Conclusions: We conclude that NOTCH1 and NOTCH2 most likely have different biological function in NSCLC. They are active in NSCLC cell lines; nonetheless both are downregulated in lung cancer cells used in this study. Moreover, NOTCH2 expression is comparatively higher than NOTCH1 expression

Human bronchial epithelial cells as a good control for evaluation potential therapeutic Notch signaling in non-small cell lung cancer

Purpose: Notch signaling is often deregulated in non-small cell lung cancer (NSCLC), but little is known about the initial endogenous mRNA status of Notch ligands and receptors. Therefore, the aim of this study was to evaluate expression level of NOTCH1 receptor and Notch ligands, such as delta like ligands (DLL1, DLL3, DLL4), and jagged ligands (JAG1, JAG2), as well as target gene-hes family bHLH transcription factor 1 (HES1) in diverse NSCLC cell lines. Materials and Methods: We have investigated the mRNA expression of chosen genes by using quantitative real time method (RT-PCR). We compared the results from NSCLC cells with results obtained in non-cancerous human bronchial epithelial cells (HBEpC). We also measured NOTCH1 expression in A549 cells, before and after treatment with γ-secretase inhibitor (GSI). Results: The expression level of NOTCH1, HES1, JAG1 and JAG2 was downregulated when compared to HBEpC. The expression of Notch ligand DLL1 was lower in all cancer cell lines, but mRNA level of DLL3 was elevated in H1299 and A549 cells when related to HBEpC. The mRNA level of DLL4 was higher in H520 and in A549 cell lines. Moreover, the mRNA level of NOTCH1 dropped down after GSI treatment, in addition A549 cells proliferated slower after drug implementation. Conclusions: We conclude that non-cancerous HBEpC cells could serve as a good control for Notch mRNAs expression analysis in NSCLC. Moreover, GSI-treated cells could inhibit proliferation through suppressing NOTCH1 in A549 cells. Keywords: Notch, NSCLC, HBEp

The arachidonate 5-lipoxygenase activating protein gene polymorphism is associated with the risk of scleroderma-related interstitial lung disease: a multicentre European Scleroderma Trials and Research group (EUSTAR) study

Contains fulltext : 174673.pdf (publisher's version ) (Closed access)Objectives.: The arachidonate 5-lipoxygenase activating protein (ALOX5AP) regulates synthesis of leukotrienes (LTs), which are important mediators of inflammation and connective tissue remodelling. The aim of this study was to evaluate if single nucleotide polymorphisms (SNPs) of ALOX5AP confer risk of SSc and/or SSc-related organ involvement. Methods.: Seven SNPs of ALOX5AP (rs17222814, rs17216473, rs10507391, rs4769874, rs9551963, rs9315050 and rs7222842) were genotyped in a cohort of 977 patients with SSc and 558 healthy controls from centres collaborating within the European Scleroderma Trials and Research group. In 22 SSc patients, concentrations of cysteinyl LTs and LT B4 (LTB4) were measured in the supernatants of ionophore-stimulated peripheral blood mononuclear cells (PBMCs) by means of commercially available enzyme immunoassay kits. Results.: Significant association was found between rs10507391 polymorphism (T/A) of ALOX5AP and the risk of SSc [odds ratio (OR) 1.27 (95% CI 1.07, 1.50), P < 0.05 vs controls], the presence of SSc-related interstitial lung disease on high-resolution CT of the lungs [OR 1.45 (95% CI 1.17, 1.79), P < 0.05 vs patients without SSc-related interstitial lung disease] as well as with restrictive ventilatory defect [forced vital capacity <70% of predicted; OR 1.51 (95% CI 1.16, 1.97), P < 0.05 vs SSc patients without pulmonary restriction]. PBMCs from SSc carriers of rs10507391 allele A synthesized greater amounts of cysteinyl LTs as compared with SSc patients with rs10507391 TT genotype ( P < 0.05). Synthesis of LTB4 did not differ significantly between the two groups. Conclusion.: The results of our study indicate that the genetic variants of ALOX5AP might play a role in the development of SSc-related pulmonary fibrosis