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Correlation between apoptosis, tumorigenesis, and levels of insulin-like growth factor I receptors
M Resnicoff1, J L Burgaud, H L Rotman
1Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Abstract:
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.
Insights
This study quantifies the link between insulin-like growth factor I receptor (IGF-IR) levels, apoptosis, and tumor growth. Reduced IGF-IR correlates with increased apoptosis and inhibited tumorigenesis in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The insulin-like growth factor I receptor (IGF-IR) plays a crucial role in cell growth and survival.
- Dysregulation of IGF-IR signaling is implicated in various cancers, including glioblastoma.
- Understanding the quantitative relationship between IGF-IR, apoptosis, and tumorigenesis is essential for developing targeted therapies.
Purpose of the Study:
- To establish a quantitative relationship between insulin-like growth factor I receptor (IGF-IR) levels, the extent of apoptosis in vivo, and tumorigenesis.
- To investigate the impact of modulating IGF-IR expression on glioblastoma cell behavior and tumor development.
- To elucidate the role of the initial apoptotic event in the timeline of transplantable tumor appearance.
Main Methods:
- C6 rat glioblastoma cells were treated with varying concentrations of antisense oligodeoxynucleotides targeting IGF-IR RNA.
- Apoptosis extent and IGF-IR levels were quantified in vivo.
- Tumorigenesis was assessed in nude mice and syngeneic rats to evaluate the fraction of surviving cells and host response.
Main Results:
- A direct correlation was observed between decreased IGF-IR levels and the extent of apoptosis in vivo.
- Tumorigenesis in nude mice was quantitatively correlated with the fraction of surviving cells after IGF-IR modulation.
- A host immune response in syngeneic rats led to complete inhibition of tumorigenesis, highlighting the importance of the tumor microenvironment.
Conclusions:
- This study provides the first quantitative evidence linking IGF-IR levels to the extent of apoptosis.
- The findings establish a quantitative relationship between the initial apoptotic event and the subsequent development of transplantable tumors.
- Modulating IGF-IR offers a potential therapeutic strategy for controlling glioblastoma growth by influencing apoptosis and host responses.