Titre du document / Document title

Insulin-like growth factor I receptor prevents apoptosis and enhances neuroblastoma tumorigenesis

Auteur(s) / Author(s)

SINGLETON J. R. ⁽¹⁾ ; RANDOLPH A. E. ⁽¹⁾ ; FELDMAN E. L. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ University of Michigan, Department of Neurology, Ann Arbor, Michigan 48109, ETATS-UNIS

Résumé / Abstract

Autocrine stimulation of the type I insulin-like growth factor receptor (IGF-IR) by IGF-II is one mechanism that allows cancer cells to maintain unregulated growth and to resist programmed cell death (PCD). SH-SY5Y and SHEP cells are cloned human neuroblastoma (NBL) lines originating from a single primary tumor. SH-SY5Y cells, which express abundant cell surface IGF-IR and produce IGF-II, exhibit serum independent growth and resist PCD due to hypoxia and hyperosmolar conditions. In contrast, SHEP cells, which produce no IGF-II and express five-fold fewer IGF-IRs, die in serum-free media or following exposure to metabolic stressors. To better understand the roles of IGF-IR and its ligand, IGF-II, in NBL carcinogenesis, we stably transfected SHEP cells with either IGF-II or IGF-IR. Unregulated expression of IGF-II did not alter the growth characteristics of SHEP/human IGF-II transfectants. In contrast, overexpression of IGF-IR allowed SHEP/IGF-IR transfectants to survive in media supplemented only by IGF-II. IGF-IR abundance correlated in a graded fashion with resistance to PCD in response to three different death-inducing paradigms: mitogen withdrawal, hyperosmolar metabolic stress, and treatment with etoposide. Our results suggest that adjuvant therapy aimed at reducing IGF-IR abundance may enhance chemotherapy-coupled apoptosis in the treatment of NBL.

Revue / Journal Title

Cancer research   ISSN 0008-5472   CODEN CNREA8 

Source / Source

1996, vol. 56, n^o19, pp. 4522-4529 (56 ref.)

Langue / Language

Anglais

Editeur / Publisher

American Association for Cancer Research, Philadelphia, PA, ETATS-UNIS  (1941) (Revue)

Mots-clés anglais / English Keywords

Neuroblastoma ; Biological receptor ; Insulin like growth factor 1 ; Transfection ; Cell proliferation ; Established cell line ; In vitro ; Autocrine secretion ; Carcinogenesis ; Tumor cell ; Human ; Nervous system diseases ; Autonomic neuropathy ; Malignant tumor ;

Mots-clés français / French Keywords

Neuroblastome ; Récepteur biologique ; Facteur croissance IGF1 ; Transfection ; Multiplication cellulaire ; Lignée cellulaire établie ; In vitro ; Sécrétion autocrine ; Carcinogenèse ; Cellule tumorale ; Homme ; Récepteur IGF1 ; Lignée SHEP ; Lignée SH-SY5Y ; Système nerveux pathologie ; Système nerveux sympathique pathologie ; Tumeur maligne ;

Mots-clés espagnols / Spanish Keywords

Neuroblastoma ; Receptor biológico ; Factor crecimiento IGF1 ; Transfección ; Multiplicación celular ; Línea celular establecida ; In vitro ; Secreción autocrina ; Carcinogénesis ; Célula tumoral ; Hombre ; Sistema nervioso patología ; Sistema nervioso simpático patología ; Tumor maligno ;

Localisation / Location

INIST-CNRS, Cote INIST : 5088, 35400006637798.0420