1. Inhibition of apoptosis by amphiregulin via an insulin-like growth factor-1 receptor-dependent pathway in non-small cell lung cancer cell lines
- Author
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Marie-Christine Favrot, Laurence Dubrez, Jean-Luc Coll, Amandine Hurbin, Groupe de Recherche sur le Cancer du Poumon, Université Joseph Fourier - Grenoble 1 (UJF), and Hurbin, Amandine
- Subjects
Time Factors ,Lung Neoplasms ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Apoptosis ,Biochemistry ,Jurkat cells ,Culture Media, Serum-Free ,Receptor, IGF Type 1 ,Jurkat Cells ,Transactivation ,Insulin-like growth factor ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Tumor Cells, Cultured ,Phosphorylation ,skin and connective tissue diseases ,Receptor ,Neutralizing antibody ,0303 health sciences ,biology ,Chemistry ,General Neuroscience ,Gefitinib ,Tyrphostins ,3. Good health ,Cell biology ,[SDV] Life Sciences [q-bio] ,030220 oncology & carcinogenesis ,Intercellular Signaling Peptides and Proteins ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,endocrine system ,EGF Family of Proteins ,animal structures ,Antineoplastic Agents ,Amphiregulin ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,History and Philosophy of Science ,Cell Line, Tumor ,medicine ,Humans ,Secretion ,Lung cancer ,Molecular Biology ,030304 developmental biology ,Glycoproteins ,Dose-Response Relationship, Drug ,Receptor Protein-Tyrosine Kinases ,Cell Biology ,medicine.disease ,Precipitin Tests ,carbohydrates (lipids) ,Kinetics ,Cell culture ,Culture Media, Conditioned ,Quinazolines ,biology.protein ,Cancer research ,Tyrosine ,HeLa Cells - Abstract
International audience; Several abnormalities in the insulin-like growth factor -1 (IGF1) and erbB receptors pathways stimulate the growth and survival of lung cancer cells, but their mechanisms of action and cooperation are poorly understood. In this report, we have identified a new mechanism of apoptosis inhibition by amphiregulin through an IGF1-dependent survival pathway in non-small cell lung cancer (NSCLC) cells: amphiregulin activates the IGF1 receptor that in turn induces the secretion of am-phiregulin and IGF1. In the absence of serum, the NSCLC cell line H358 resists apoptosis and secretes factors protecting the NSCLC cell line H322 from serum deprivation apoptosis. IGF1 receptor inhibitor AG1024 as well as epidermal growth factor receptor inhibitors AG556 and ZD1839 restore apoptosis in H322 cells cultured in H358-conditioned medium. Accordingly, the an-ti-apoptotic activity of H358-conditioned medium is completely abolished after incubation with anti-amphi-regulin neutralizing antibody and only partially with anti-IGF1 neutralizing antibody. H358-conditioned medium and amphiregulin induce IGF1 receptor phospho-rylation in H322 cells, which is prevented by anti-amphi-regulin neutralizing antibody but not by AG556 or ZD1839. H358 cells secrete a high level of amphiregulin that, in combination with IGF1, prevents serum deprivation apoptosis. Finally, IGF1 receptor inhibitor blocks amphiregulin and IGF1 release by H358 cells.
- Published
- 2004
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