Background The epidermal growth factor receptor consists selleck of an extracellular ligand binding domain, a transmembrane domain and an intracellular tail with an ATP binding site, tyrosine kinase activity, and capability of autophosphoryl ation. EGFR has been found to contribute the lung development and multiplicity of cancer Inhibitors,Modulators,Libraries related signal transduction pathways like cellular proliferation, adhesion, migration, neoangiogenesis, and apoptosis inhibition. EGFR is also responsible for the sensitivity of human non small cell lung cancer cells to therapies and prognosis of patients. There are numerous ligands to bind with EGFR, such as EGF, transforming growth factor. heparin binding EGF like growth factor, epiregulin, amphiregulin, neuregulin subfamily and betacellulin.
The activation of EGFR can initiate the downstream signaling cascades, e. g. the Rasmitogen Inhibitors,Modulators,Libraries activated protein kinase and phosphoinositide 3 kinase Akt. BTC is a member of EGF family and acts as a potent mitogen for cell types, with the higher affinity and specifi city for ErbB1EGFR and ErbB4. Homologous or heterol ogous dimers of ErbB family receptor Inhibitors,Modulators,Libraries are then formed to activate signal transduction pathways, such as PI3K PDK1Akt and RASRAFMEKErk, leading to a series of biological effects. Abnormal phosphorylation of Akt and Erk12 was considered as an important fac tor in the prognosis of cancer and constitutive acti vation of EGFRAktmTOR was found in about 18% of NSCLCs.
Our previous study on disease specific biomarkers of pa tients with acute exacerbations of chronic obstructive pul monary disease Inhibitors,Modulators,Libraries by integrating inflammatory mediators with clinical informatics demonstrated that BTC played an important role in the occurrence of AECOPD and was associated with the disease severities. We also found that EGFRPI3KAktErk pathway was involved in the development of lung cancer inflammatory microenvir onment by the hyper production of CXCL8, respon sible for leukocyte recruitment, cancer proliferation, and angiogenesis. The present study further aimed at understanding the potential association and interaction mechanisms between BTC and CXCL8 in the inflammatory microenvironment, exploring the expression and biological function of BTC gene and protein and its receptors in hu man lung cancer cells, and define the role of BTC in the regulation of CXCL8 expression and production in lung cancer.
The present study Inhibitors,Modulators,Libraries furthermore investigated the in volvement of EGFRPI3KAktErk activation in CXCL8 production induced by BTC with consequences on lung cancer cell proliferation and movement. Materials and methods Cell lines and reagents Human lung cancer cell line A549 cells were cultured in RPMI 1640 supplemented with penicillin, streptomycin, and 10% heat inactivated fetal bovine serum. Human recombinant BTC, Enzyme selleck chem inhibitor Linked Immunosorbent Assay kits for CXCL8, anti human BTC neutralizing antibody were purchased from R D Systems.