Gastrointestinal hormones stimulate growth of Foregut Neuroendocrine Tumors by transactivating the EGF receptor

► In BON and QGP cells, various GI hormones/neurotransmitters stimulated growth (bradykinin, Bombesin, PACAP, Neurotensin). ► NET growth by the GI hormones neurotransmitters was inhibited by AG1478, an EGFR inhibitor. ► Each of the GI hormones/neurotransmitters stimulated EGFR transactivation with Y1068 tyrosine phosphorylation of the EGFR. ► EGFR transactivation required activation of Src kinases, PKC and matrix metalloproteinases. ► EGFR transactivation required activation of reactive oxygen species.