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Autocrine stimulation by insulin-like growth factor I is involved in the growth, tumorigenicity and chemoresistance of human esophageal carcinoma cells.
- Source :
-
Journal of biomedical science [J Biomed Sci] 2002 Nov-Dec; Vol. 9 (6 Pt 2), pp. 665-74. - Publication Year :
- 2002
-
Abstract
- Insulin-like growth factor I (IGF-I) receptor (IGF-IR)-mediated signals are known to be involved in cell growth and transformation and prevention of apoptosis. In this study, we demonstrated the coexpression of IGF-I and IGF-IR in human esophageal carcinoma tissues. We also demonstrated the IGF-I autocrine system in esophageal carcinoma cell lines. Both the CE48T/VGH and CE81T/VGH cell lines showed proliferative responses to IGF-I stimulation. Autokinase activity of IGF-IR in these cells can be triggered by the exogenous addition of IGF-I. In addition, an IGF-I peptide antagonist, JB1, specifically inhibited ligand-induced receptor autophosphorylation in a dose-dependent manner. Under serum-free conditions, JB1 also reduced the degree of IGF-IR phosphorylation and cell numbers. Furthermore, the addition of JB1 decreased the number of CE81T/VGH colonies formed in methyl cellulose agar and the size and the incidence of tumors which grew in mice with severe combined immunodeficiency. These results imply that an IGF-I autocrine system in human esophageal carcinoma cells could stimulate tumor growth. Finally, we found that IGF-I prevented the apoptosis of CE81T/VGH cells induced by chemotherapeutic drugs, such as cisplatin, 5-fluorouracil and camptothecin. Thus, interruption of IGF-IR function may provide a way to retard tumor growth and increase the sensitivity of esophageal carcinoma to chemotherapy.<br /> (Copyright 2002 National Science Council, ROC and S. Karger AG, Basel)
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Apoptosis drug effects
Cell Division drug effects
Drug Interactions
Esophageal Neoplasms drug therapy
Humans
Insulin-Like Growth Factor I analysis
Insulin-Like Growth Factor I antagonists & inhibitors
Mice
Mice, SCID
Phosphorylation
Receptor, IGF Type 1 analysis
Transplantation, Heterologous
Tumor Cells, Cultured
Autocrine Communication drug effects
Drug Resistance, Neoplasm
Esophageal Neoplasms chemistry
Insulin-Like Growth Factor I pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1021-7770
- Volume :
- 9
- Issue :
- 6 Pt 2
- Database :
- MEDLINE
- Journal :
- Journal of biomedical science
- Publication Type :
- Academic Journal
- Accession number :
- 12432233
- Full Text :
- https://doi.org/10.1159/000067282