Potential molecular mechanisms of insulin like growth factor-1 (IGF-1)/insulin like growth factor-1 receptor (IGF-1R) interaction in prostate cancer invasion
Bibliographic record
Abstract
5030 Epidemiological studies suggest that elevated serum levels of the peptide growth factor, IGF-1 is linked to an increased risk of developing prostate cancer. However, little is known about a direct role of IGF-1/IGF-1R axis in prostate cancer progression to an invasive phenotype. The objective of this study is to investigate the role of IGF-1/IGF-1R in regulating the invasive phenotype of prostate cancer and evaluate the molecular mechanism/s involved in promoting this invasive potential. Binding of IGF-1 to its receptor IGF-1R is known to signal intracellularly via the phosphatidylinositol 3-kinase (PI3-K) pathway and the p42/44 mitogen activated protein kinase (MAPK) pathway. Invasion assays using Matrigel invasion chambers indicate that treatment of DU145 human prostate carcinoma cells with IGF-1 results in an increase in invasive potential of these cells and this stimulation is attenuated in the presence of the PI3-K inhibitor Wortmannin (W) and with the MAPK inhibitor PD98059 (PD). IGF-1 stimulation is also inhibited in the presence of an IGF-1R neutralizing antibody indicating the invasive phenotype of DU145 cells is due specifically to IGF-1 stimulation. The activities of the PI3-K and MAPK pathways, as determined by phosphorylation of protein kinase B and p42/44 MAP kinase respectively, indicated that both pathways are activated in the presence of IGF-1 and this stimulatory effect is inhibited in the presence of their inhibitors W and PD respectively. IGF-1/IGF-1R mediated regulation of the expression of matrix metalloproteinases (MMPs) was evaluated as a mechanism involved in promoting the invasive phenotype. Gelatin zymography identified that the activities of MMP-2 and –9 (two gelatinases highly associated with prostate cancer invasion) were stimulated by IGF-1 while MMP-1 activity remained unaltered. IGF-1 activation of MMP-2 and –9 was inhibited in the presence of W and PD. Western blot analysis of MMP-2 and MMP-9 protein expression showed that while MMP-9 expression paralleled the zymogram results, there was no change in MMP-2 expression. This indicates that while IGF-1 regulation of MMP-9 activity may be at the transcriptional level, MMP-2 is likely regulated by other mechanism/s. These results suggest that IGF-1 is involved in promoting prostate cancer invasion by regulating MMP-2 and 9 expression and activities through the PI3-K and MAPK pathways. (This research was supported by funds from the Hamilton Health Science research foundation).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".