NF-κB Fans the Flames of Lung Carcinogenesis

Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Cancer Prevention Research (Impact Factor: 4.44). 03/2010; 3(4):403-5. DOI: 10.1158/1940-6207.CAPR-10-0042
Source: PubMed


This perspective on Deng et al. (beginning on p. 424 in this issue of the journal) examines the link between NF-kappa B and lung tumorigenesis. Experiments in genetically engineered mouse models of lung cancers are elucidating protumorigenic roles of NF-kappa B activation in lung cancer pathogenesis. Our growing understanding of the tumor-promoting NF-kappa B downstream effector pathways could lead to the development of novel approaches for lung cancer therapy and chemoprevention. Cancer Prev Res; 3(4); 403-5. (C)2010 AACR.

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    • "NF-κB regulated genes include cytokines, adhesion molecules, angiogenic factors, anti-apoptotic factors, and matrix metalloproteinases (MMPs), which are involved in different steps of carcinogenesis. It has been suggested that NF-κB promotes lung cancer mainly through mediating inflammatory cytokines secretion to establish a cancer-prone inflammatory microenvironment [48]. Similarly, NF-κB pathways play a crucial role in the pathogenesis/development of COPD by increasing the release of pro-inflammatory mediators leading to chronic inflammation in the lung. "
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    ABSTRACT: Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.
    International Journal of Molecular Sciences 02/2013; 14(2):3440-55. DOI:10.3390/ijms14023440 · 2.86 Impact Factor
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    • "Nuclear factor kappaB (NF-kB) plays a critical role in several biological processes, including cell cycle regulation [1e3], expression of specific genes [4] [5], regulation of cell differentiation [6] [7] and apoptosis [8e11]. On the other hand, alteration of NF-kB activity is associated with several human pathologies, including osteoporosis [12], rheumatoid arthritis [13] and cancer [14] [15]. In addition, NF-kB is one among the master transcription factors responsible for inflammation in cystic fibrosis (CF) cells infected with Pseudomonas aeruginosa [16e20]. "
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    ABSTRACT: Nuclear Factor kappaB (NF-κB) plays a very important role in the control of gene expression and is deeply involved in several human pathologies. Accordingly, molecules targeting NF-κB dependent biological functions are considered of great interest. Virtual screening of furocoumarin libraries against NF-κB p50 allowed to rank compounds in respect to their expected ability to bind NF-κB and the identified compound might be considered for the development of analogs to be tested for biological activity on inhibition of NF-κB/DNA complex formation. The data reported in the present paper suggest that, following this approach, the best ranked compounds identified by virtual screening (a) strongly bind in silico to NF-κB and (b) efficiently inhibit the molecular interactions between (32)P-labeled NF-κB double stranded DNA and p50 or p50/p65 complex. These data allowed to develop a novel lead of great interest for inhibiting NF-κB dependent biological functions. This novel molecule (compound 2), bearing a methyl group in the 9 position of the psoralen nucleus, exhibits high efficiency in inhibiting NF-κB/DNA interactions. In addition, we found that compound 2 is a potent inhibitor of IL-8 gene expression in TNF-α treated IB3-1 cystic fibrosis cells. Taken together, our data indicate that compound 2 might find an important place in the set of molecules of interest for the development of pharmaceutical strategies against the inflammatory phenotype of cystic fibrosis.
    European Journal of Medicinal Chemistry 07/2011; 46(10):4870-7. DOI:10.1016/j.ejmech.2011.07.032 · 3.45 Impact Factor
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    ABSTRACT: Cancer prevention encompasses a wide range of highly developed science and clinical impact. Enunciating these two aspects in the same breath highlights the crucial link between them. The breadth and excitement of current opportunities in the science of cancer prevention have never been greater. Major avenues of such research include the extent and effect of premalignancy, the molecular underpinnings of carcinogenesis and related prevention targets, in vitro model systems of the progression of normal human epithelial cells to tumorigenesis, molecular risk stratification and pharmacogenomic approaches, and many more. We describe the clinical impacts of cancer prevention (with examples in the areas of molecular targeting, vaccines, epidemiology, and behavioral science) and the stage-setting science that facilitated them. In addition, discussed are new prevention opportunities such as interactions between stromal and microenvironmental factors, the control of premalignant stem cell phenotypes through epigenetic reprogramming, and neoplastic cells and various stress responses including those involving telomere biology. The promise of this science, particularly integrative, interdisciplinary research, is to hasten the ability of clinical prevention to reduce the burden of cancer.
    Cancer Prevention Research 03/2010; 3(4):394-402. DOI:10.1158/1940-6207.CAPR-10-0051 · 4.44 Impact Factor
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