The DEGs (<i>IL6, MDM2, CDC42</i> and <i>MAX</i>) involved in different pathways, including the p53 signaling pathway and endocytosis, may be the potential targets for DAMTC in lung adenocarcinoma.
Subsequently, cells were co-cultured with a lung adenocarcinoma cell line (A549 cells) to evaluate the effects on proliferation, oncogene expression and IL6 secretion.
These results suggest a possible role of tumoral expression for IL-6R in LUAD, which means it may have potential as a prognostic marker for this type of cancer.
Our findings indicate that downregulation of miR-425 caused by IL-6/STAT3 signaling leads to loss of ADAM9 targeting, results in enhanced ADAM9 expression, and contributes to the development of lung adenocarcinoma.
We undertook a detailed assessment of the IL-6/JAK1/phosphorylated STAT3 (pSTAT3) pathway in resected lung adenocarcinoma specimens, with special interest in whether the presence of an EGFR mutation enriched for pSTAT3 positivity.
In the discovery stage, haplotype GGG in three SNPs (rs2069840, rs2069852, rs2066992) of IL-6, synergetic effects of IL-6rs2069840 and environmental tobacco smoke in the workplace were found to be related to EGFR mutant lung adenocarcinoma.
Our results offer a preclinical rationale to clinically evaluate IL6 trans-signaling as a therapeutic target for the treatment of KRAS-driven lung adenocarcinoma.
As NFκB inhibitor and knockdown RelA expression greatly reduced constitutive AhR-induced IL-6 expression, we hypothesized that AhR expression, in the absence of exogenous ligand, is able to modulate NFκB activity and subsequently upregulate IL-6 expression, thus promoting the development of lung AD.
Inhibitors of Jak2/Stat3, MEK/Erk and PI3-K/Akt pathways down-regulated IL-6 secretion in the lung adenocarcinoma PC14PE6/AS2 (AS2) cells, which spontaneously secreted IL-6 and possessed constitutively activated Stat3.
It is concluded that the JAK2/STAT3 pathway is involved in the IL-6-mediated regulation of MMP-10, and IL-6 can moderately reduce MMP-10 mRNA levels and strongly increase MMP-10 protein mass in human lung adenocarcinoma A549 cells.
Treatment of cultured human lung adenocarcinoma epithelial cells (A549) with IHR resulted in the elevation of mRNA levels of an inflammation cytokine interleukin-6 (IL-6), due to activation of the signaling pathway of nuclear factor-kappaB, a potent transcriptional activator of IL-6.
Therefore, mutant EGFR could activate the gp130/JAK/STAT3 pathway by means of IL-6 upregulation in primary human lung adenocarcinomas, making this pathway a potential target for cancer treatment.
In this issue of the JCI, two reports provide intriguing new information on the role of the inflammatory cytokine IL-6 in breast and lung cancer.The study by Sansone et al. implicates IL-6 in the instigation of malignant properties in breast cancer stem cells (see the related article beginning on page 3988).The study by Gao et al. identifies mutant variants of EGFR as inducers of IL-6 in lung adenocarcinomas (see the related article beginning on page 3846).
This study has determined the ability of MEP to alter the expression of select genes from drug metabolism, cytokine, oncogene, tumor suppressor, and estrogen signaling families of human lung adenocarcinoma CL5 cells. cDNA microarray analyses and confirmation studies were performed using CL5 cells treated with 100 microg/ml MEP extract for 6 h. The results showed that MEP increased the mRNA levels of metabolic enzymes CYP1A1 and CYP1B1, proinflammatory cytokines interleukin (IL)-1alpha, IL-6, and IL-11, fibroblast growth factor (FGF)-6 and FGF-9, vascular endothelial growth factor (VEGF)-D, oncogene fra-1, and tumor suppressor p21.
These data demonstrate that cytokines of the IL-6 group have potential as differentiation inducers in lung adenocarcinoma cells and that there is an equivalent paracrine factor(s) in lung fibroblast conditioned medium.
Analysis of 5'-deletion mutants and the full length Ax 1 promoter fused to a luciferase reporter gene using transient transfections of human lung adenocarcinoma A 549 cells identified a unique 30 bp region of the Ax 1 promoter as critical for the responsiveness of the reporter gene to IL-6 and dexamethasone.
A human hepatoblastoma cell line (C3A, a subclone of HepG2/C3 that is currently being used as a surrogate liver) and human lung adenocarcinoma cells (A549) were stimulated with interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma), or IL-6 to determine any differences in cell type responsiveness to individual cytokines for ICAM-1 upregulation.