ArticleAmerican journal of respiratory cell and molecular biology2007
EGFR signaling is required for TGF-beta 1 mediated COX-2 induction in human bronchial epithelial cells.
Article in American journal of respiratory cell and molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Amphiregulin and Fibrosis: Existing Evidence and Future Directions.International journal of molecular sciences · 2025Review
- Administration of a combination of COX-2/TGF-β1 siRNAs induces hypertrophic scar fibroblast apoptosis through a TP53 mediated caspase pathway.Scientific reports · 2024Article
- Tonic ErbB signaling underlies TGFβ-induced activation of ERK and is required for lens cell epithelial to myofibroblast transition.Molecular biology of the cell · 2024Article
- Activation of TRPV4 Regulates Respiration through Indirect Activation of Bronchopulmonary Sensory Neurons.Frontiers in physiology · 2016Article
- Article
- Human airway smooth muscle cells secrete amphiregulin via bradykinin/COX-2/PGE2, inducing COX-2, CXCL8, and VEGF expression in airway epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Macrophage migration inhibitory factor (MIF) enzymatic activity and lung cancer.Molecular medicine (Cambridge, Mass.) · 2015Article
- TGFβ can stimulate the p(38)/β-catenin/PPARγ signaling pathway to promote the EMT, invasion and migration of non-small cell lung cancer (H460 cells).Clinical & experimental metastasis · 2014Article
- The Effect of Helicobacter pylori on Epidermal Growth Factor Receptor-Induced Signal Transduction and the Preventive Effect of Celecoxib in Gastric Cancer Cells.Gut and liver · 2013Article
- Amphiregulin, an epidermal growth factor receptor ligand, plays an essential role in the pathogenesis of transforming growth factor-β-induced pulmonary fibrosis.The Journal of biological chemistry · 2012Article
- Expression levels of estrogen receptor beta in conjunction with aromatase predict survival in non-small cell lung cancer.Lung cancer (Amsterdam, Netherlands) · 2011Article
- [Advances of targeted therapy based on estrogen receptor signaling pathway in lung cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2011Review
- Regulation of the arachidonic acid mobilization in macrophages by combustion-derived particles.Particle and fibre toxicology · 2011Article
- Small molecule inhibitors of the host cell COX/AREG/EGFR/ERK pathway attenuate cytomegalovirus-induced pathogenesis.Experimental and molecular pathology · 2011Article
- EGFR and COX-2 protein expression in non-small cell lung cancer and the correlation with clinical features.Journal of experimental & clinical cancer research : CR · 2011Article
- The role of prostaglandin E2 (PGE 2) in toll-like receptor 4 (TLR4)-mediated colitis-associated neoplasia.BMC gastroenterology · 2010Article
- Tracheal Basal cells: a facultative progenitor cell pool.The American journal of pathology · 2010Article
- PGE(2) contributes to TGF-beta induced T regulatory cell function in human non-small cell lung cancer.American journal of translational research · 2010Article
- Activation of macrophage peroxisome proliferator-activated receptor-gamma by diclofenac results in the induction of cyclooxygenase-2 protein and the synthesis of anti-inflammatory cytokines.Molecular and cellular biochemistry · 2009Article
- Targeting aromatase and estrogen signaling in human non-small cell lung cancer.Annals of the New York Academy of Sciences · 2009Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Cyclooxygenase-2 (COX-2) is a key enzyme in the production of prostaglandins and thromboxanes from free arachidonic acid. Increasing evidence suggests that COX-2 plays a role in tumorigenesis. A variety of stimuli induce COX-2 and it is overexpressed in many tumors, including non-small cell lung cancer (NSCLC). We studied the regulation of COX-2 expression in immortalized human bronchial epithelial cells (HBECs) by transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF) because these two growth factors are present in both the pulmonary milieu of those at risk for lung cancer as well as in the tumor microenvironment. EGF significantly enhanced TGF-beta1-mediated induction of COX-2 and corresponding prostaglandin E2 (PGE2) production. TGF-beta1 and EGF induced COX-2 at the transcriptional and post-transcriptional levels. EGF receptor (EGFR) inhibition, neutralizing antibody against amphiregulin, or mitogen-activated protein kinase kinase (MEK) inhibition blocked TGF-beta1-mediated COX-2 induction. COX-2 induction by TGF-beta1 depended upon Smad3 signaling and required the activity of EGFR or its downstream mediators. Autocrine amphiregulin signaling maintains EGFR in a constitutively active state in HBECs, allowing for COX-2 induction by TGF-beta1. Thus, EGFR ligands, which are abundant in the pulmonary microenvironment of those at risk for lung cancer, potentiate and are required for COX-2 induction by TGF-beta1 in HBEC. These findings emphasize the central role of EGFR signaling in COX-2 induction by TGF-beta1 and suggest that inhibition of EGFR signaling should be investigated further for lung cancer prevention.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.