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Neurotensin (NTS)-like peptides are autocrine growth factors for lung cancer. NTS is present in and secreted from lung cancer cells and binds to G protein-coupled receptors causing signal transduction and proliferation. The growth of non-small cell lung cancer (NSCLC) cells is stimulated by NTS and inhibited by SR48692, a small molecule NTSR1 antagonist. Adding NTS to NSCLC cells increases the tyrosine phosphorylation of ErbB receptor tyrosine kinases EGFR, HER2, and HER3 by transactivation. The NTSR1 regulation of EGFR, HER2, and HER3 transactivation is blocked by SR48692, specific tyrosine kinase inhibitors, and certain monoclonal antibodies. Additional agents which impair the transactivation process include PP2 (Src inhibitor), GM6001 (matrix metalloprotease inhibitor), and N-acetyl-cysteine (antioxidant). The results indicate growth stimulation caused by the adding NTS to NSCLC cells may be mediated by transactivation of ErbB RTKs.
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