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Neuromedin B causes transactivation of Epidermal Growth Factor receptors in lung cancer cells
Author(s) -
Moody Terry W,
Berna Marc,
Mantey Samuel,
Jensen Robert
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1150-b
Subject(s) - transactivation , epidermal growth factor , autocrine signalling , epidermal growth factor receptor , bombesin , mapk/erk pathway , phosphorylation , tyrosine phosphorylation , endocrinology , cancer research , chemistry , medicine , receptor , biology , microbiology and biotechnology , biochemistry , transcription factor , neuropeptide , gene
The transactivation of Epidermal Growth Factor receptors (EGF‐Rs) was investigated in lung cancer cells. Neuromedin B (NMB), which is an autocrine growth factor in some lung cancer cells (Moody et al., JPET 1992;163:), has structural homology with bombesin (BB) and gastrin releasing peptide (GRP). Also, some lung cancer cells have EGF‐R overexpression and/or mutation. Here the ability of NMB to transactivate EGF‐Rs was investigated by Western blot. Ten nM NMB or BA0, a universal agonist, but not BB or GRP caused phosphorylation of Tyr1068 of the EGF‐R using NCI‐H1299 cells. This signal was amplified using NCI‐H1299 cells stably transfected with NMB‐Rs. The transactivation of EGF‐Rs or the phosphorylation of ERK caused by NMB was inhibited by AG1478, a tyrosine kinase inhibitor, as well as PD168368, a NMB‐R antagonist, but not BW2258U89, a GRP‐R antagonist. These results suggest that NMB causes ERK activation after phosphorylation of the EGF‐Rs in lung cancer cells. Also, the transactivation of the EGFR caused by NMB addition to lung cancer cells was inhibited by GM6001, a matrix metalloprotease inhibitor. It remains to be determined if NMB causes release of EGF‐R agonists from lung cancer cells, such as transforming growth factor alpha, resulting in tyrosine phosphorylation of EGF‐Rs.