Correlation between apoptosis, tumorigenesis, and levels of insulin-like growth factor I receptors.
We have investigated whether there is a quantitative relationship between the insulin-like growth factor I receptor (IGF-IR), the extent of apoptosis in vivo, and tumorigenesis. C6 rat glioblastoma cells were treated with increasing concentrations of antisense oligodeoxynucleotides to the IGF-IR RNA. The extent of apoptosis in vivo is correlated to the decrease in IGF-IR levels and, in turn, tumorigenesis in nude mice is correlated to the fraction of surviving cells. In syngeneic rats, a host response leads to complete inhibition of tumorigenesis. These findings establish, for the first time on a quantitative basis, the relationship between IGF-IR levels and the extent of apoptosis, as well as the relationship between the initial apoptotic event and the time of appearance of transplantable tumors.
Resnicoff
M
M
Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Burgaud
J L
JL
Rotman
H L
HL
Abraham
D
D
Baserga
R
R
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006085:Graft Survival; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000209:etiology*; D016376:Oligonucleotides, Antisense / Q000378:metabolism*; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D017526:Receptor, IGF Type 1