NF-κB

Gene Variant Linked With Reduced Lung Cancer Risk.

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A variant in a gene involved with inflammation and the immune response is linked with a decreased risk of lung cancer. That is the finding of an analysis published early online in CANCER, a peer-reviewed journal of the American Cancer Society. The results add to the growing body of literature implicating these processes in the development of lung cancer.

Meredith Shiels, PhD, MHS and Anil Chaturvedi, PhD, of the National Cancer Institute in Rockville, MD, and their colleagues analyzed 1,429 variants in inflammation- and immunity-related genes from 378 patients with lung cancer and 450 healthy controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial. The investigators observed a significant link between lung cancer and 81 single nucleotide polymorphisms (SNPs) located in 44 genes.

They then compared these results with observed or imputed data from four recently completed genome-wide association studies (GWAS) that included 5,739 lung cancer cases and 5,848 controls. Of the 81 SNPs, one in particular — named rs4648127 and located within the NFKB1 gene — was associated with lung cancer in both analyses. This SNP was linked with an estimated 44 percent reduced risk of lung cancer in the cancer screening trial and a 21 percent reduced risk in the combined GWAS analysis.

The NF-κB, or nuclear factor kappa B, protein that is produced in part from the NFKB1 gene is known to play an important role in immunity and inflammation by regulating gene expression, cell death, and cell proliferation. Also, previous research has shown that immunity and inflammation may affect the development of lung cancer. “Our study provides further evidence that inflammation may be associated with lung cancer risk,” said Dr. Shiels. She added that future studies should further examine the NFKB1 gene and its relationship with lung cancer risk.

Source: http://www.sciencedaily.com

 

Rapid Activation of Stat3 and ERK1/2 by Nicotine Modulates Cell Proliferation in Human Bladder Cancer Cells.

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Cigarette smoke is a major risk factor for bladder cancer. The main component in cigarette smoke, nicotine, can be detected in the urine of smokers. Nicotine has been implicated as a cocarcinogen that promotes lung cancer development through prosurvival pathways. Although the mechanisms of nicotine-induced cell proliferation have been well studied in lung epithelial cells, the molecular mechanism of its action in bladder epithelial cells is still unclear. The aims of this study were to investigate whether there is nicotine-induced bladder epithelial cell proliferation and to identify the signaling transduction pathway regulated by nicotine. We found that nicotine simultaneously activates Stat3 and extracellular signal regulated kinase 1/2 (ERK1/2) in T24 cells. Stat3 activation via nicotinic acetylcholine receptor (nAChR)/protein kinase C signaling pathway was closely linked to Stat3 induction and nuclear factor-κB DNA binding activity, which is associated with Cyclin D1 expression and cell proliferation. ERK1/2 activation through nAChR and β-adrenoceptors plays a dual role in cell proliferation; it phosphorylates Stat3 at Ser727 and regulates cell proliferation. We conclude that through nAChR and β-adrenoceptors, nicotine activates ERK1/2 and Stat3 signaling pathways, leading to Cyclin D1 expression and cell proliferation. This is the first study to investigate signaling effects of nicotine in bladder cells. The current findings suggest that people exposed to nicotine could be at risk for potential deleterious effects, including bladder cancer development.