Bombesin receptors regulate EGFR transactivation in cancer

Abstract

Bombesin (BB)-like peptides are autocrine growth factors for small cell lung cancer (SCLC), a neuroendocrine tumor.  BB-like peptides are present in and secreted from SCLC cells, where they bind to cell surfact G protein coupled receptors (GPCR).  When the BB2R is activated it interacts with a G-protein (Gq) causing signal transduction mechanisms which lead to increased cellular proliferation.  The growth of SCLC is inhibited by BB2R antagonists.  In Non-SCLC (NSCLC) cells, but not SCLC cells, the receptor tyrosine kinase (RTK) for epidermal growth factor (EGF) predominates.  Addition of NMB to NSCLC cells, causes tyrosine phosphorylation of the EGFR through a process called transactivation.  The EGFR transactivation caused by NMB addition to NSCLC cells is inhibited by BB1R antagonists and EGFR tyrosine kinase inhibitors (TKI) such as gefitinib or erlotinib.  BB1R antagonists are synergistic with gefitinib at inhibiting NSCLC growth.  The BB1R may regulate the growth of NSCLC, an epithelial tumor, in an EGFR-dependent manner.