The insulin-like growth factor I receptor protects tumor cells from apoptosis in vivo.
The role of the insulin-like growth factor I receptor (IGF-IR) in programmed cell death has been investigated in vivo in a biodiffusion chamber, where the extent of cell death could be determined quantitatively. We found that a decrease in the number of IGF-IRs causes massive apoptosis in vivo in several transplantable tumors, either from humans or rodents. Conversely, an overexpressed IGF-IR protects cells from apoptosis in vivo. We also show that the same conditions that in vitro cause only partial growth arrest with a minimum of cell death, induce in vivo almost complete cell death. We conclude that the IGF-IR activated by its ligands plays a very important protective role in programmed cell death, and that its protective action is even more striking in vivo than in vitro.
Resnicoff
M
M
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Abraham
D
D
Yutanawiboonchai
W
W
Rotman
H L
HL
Kajstura
J
J
Rubin
R
R
Zoltick
P
P
Baserga
R
R
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D015194:Diffusion Chambers, Culture; D005909:Glioblastoma / Q000473:pathology* / Q000648:ultrastructure*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D017526:Receptor, IGF Type 1