Antagonists of growth hormone releasing hormone and bombesin inhibit the expression of EGF/HER receptor family in H-69 small cell lung carcinoma

• Published in: Cancer letters 2005-08, Vol.226 (2), p.123-131
• Main Authors: Kanashiro, Celia A., Schally, Andrew V., Varga, Jozsef L., Hammann, Brian, Halmos, Gabor, Zarandi, Marta
• Format: Article
• Language: English
• Subjects: Binding sites; Blotting, Western; Bombesin - antagonists & inhibitors; Bombesin/GRP; Cancer; Cancer therapy; Carcinoma, Small Cell - metabolism; Cell Line, Tumor; EGFR; Epidermal growth factor; GHRH antagonists; Growth Hormone-Releasing Hormone - antagonists & inhibitors; GRP antagonist; HER; Humans; Insulin-like growth factors; Kinases; Ligands; Lung Neoplasms - metabolism; Medical prognosis; Peptides; Pituitary gland; Proteins; Receptor, Epidermal Growth Factor - biosynthesis; Receptor, Epidermal Growth Factor - drug effects; Receptor, ErbB-2 - biosynthesis; Receptor, ErbB-2 - drug effects; Receptor, ErbB-3 - biosynthesis; Receptor, ErbB-3 - drug effects; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Rodents; Studies; Tumors; Veterans
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2005.01.008

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.