Antagonists of growth hormone releasing hormone and bombesin inhibit the expression of EGF/HER receptor family in H-69 small cell lung carcinoma.
Effects of in vivo treatment with antagonists of growth hormone-releasing hormone (GHRH), JV-1-65 and MZ-J-7-110, and bombesin/gastrin-releasing peptide antagonist RC-3940-II, on the EGF receptor (EGFR) family, were investigated in H-69 SCLC. Tumors were analyzed by RT-PCR, immunoblotting and binding assays. Treatment with these analogs reduced the binding capacity of EGFR by 18-64%, and inhibited the mRNA expression for EGFR, HER-2 and -3 by 27-75.4, 17-26.3, and 13.8-46.6%, respectively. The antagonists also decreased the protein levels for EGFR by 21-34%, HER-2 by 36-68% and HER-3 by 43-49%. This is the first demonstration that antiproliferative effects of GHRH antagonists are associated with a downregulation of EGF/HER receptors.
Kanashiro
Celia A
CA
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, 1601 Perdido Street, New Orleans, LA 70112, USA.
Schally
Andrew V
AV
Varga
Jozsef L
JL
Hammann
Brian
B
Halmos
Gabor
G
Zarandi
Marta
M
D015153:Blotting, Western; D001839:Bombesin / Q000037:antagonists & inhibitors*; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000096:biosynthesis / Q000187:drug effects*; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000187:drug effects; D020893:Receptor, ErbB-3 / Q000096:biosynthesis / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001839:Bombesin; D066246:ErbB Receptors; D013007:Growth Hormone-Releasing Hormone; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3