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Journal of Biomedical Science

, Volume 9, Issue 6, pp 665–674 | Cite as

Autocrine stimulation by insulin-like growth factor I is involved in the growth, tumorigenicity and chemoresistance of human esophageal carcinoma cells

  • Young-Chau Liu
  • Chuen-Miin Leu
  • Fen-Hwa Wong
  • Wan-Shung Fong
  • Shan-Chun Chen
  • Chungming Chang
  • Cheng-po Hu
Original Paper

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.

Key Words

Insulin-like growth factor I Esophagus Carcinoma Tumorigenicity Chemotherapy 

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Copyright information

© National Science Council 2002

Authors and Affiliations

  • Young-Chau Liu
    • 2
    • 4
  • Chuen-Miin Leu
    • 2
  • Fen-Hwa Wong
    • 3
  • Wan-Shung Fong
    • 1
  • Shan-Chun Chen
    • 2
  • Chungming Chang
    • 1
    • 2
  • Cheng-po Hu
    • 1
    • 2
  1. 1.Department of Medical Research and EducationVeterans General Hospital-TaipeiTaipeiTaiwan (ROC)
  2. 2.Institute of Microbiology and ImmunologyTaiwan, ROC
  3. 3.Institute of Public HealthNational Yang-Ming UniversityTaipei
  4. 4.College of Liberal EducationShu-Te UniversityKaohsiungTaiwan, ROC

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