The influence of growth hormone/insulin-like growth factor deficiency on prostatic dysplasia in pbARR2-cre PTEN knockout mice.
Bibliographic record
Abstract
66 Background: Signaling through GH/IGF-I axis has been linked to PCa risk. The GH/IGF-I axis is an important regulator of growth, survival, and metastatic potential in a variety of malignancies and is strongly implicated in PCa etiology. A range of therapeutic approaches including reducing ligand availability by GH antagonist, IGF-I antibodies, and recombinant IGFBPs, reducing IGF-1R expression by antisense and RNA interference, or inhibiting of IGF-1R signaling by IGF-1R antibodies and small molecule tyrosine kinase inhibitors are under investigation in PCa. Methods: To investigate the role of GH/IGF-I axis on in vivo prostate carcinogenesis and neoplastic progression, we crossed pbARR2-Cre, PTEN(fl/fl) mice (PTEN-/-) with IGF-I deficient lit mice, and produced lit/lit and lit/+ PTEN-/- mice. To complement the in vivo experiments, in vitro growth and growth factor signaling of murine PTEN-/- cells derived from the prostate (MPPK) using serum from lit/lit or lit/+ mice was examined. Results: No obvious differences in prostatic dysplasia were observed in lit/lit mice at 15 and 20 weeks of age when compared to lit/+ littermates measured as normalized prostatic wet weight or for expression of the murine prostatic differentiation markers, probasin and PSP94. However the rate of decreased expression of E-cadherin and increased expression of N-cadherin was slightly delayed in PTEN-/- prostates from lit/lit mice as compare to lit/+ mice. In vitro, growth of MPPK cells was decreased when cultured in serum from lit/lit mice as compared with serum from lit/+ mice. Suppressed growth of MPPK cells in lit/lit serum could be restored by addition of IGF-I, and to a lesser extent, GH. Addition of GH or IGF-I to lit/lit serum increased steady-state activation of AKT without affecting ERK1/2 activation. Conclusions: Our data suggest that initiation of prostate carcinogenesis by loss of PTEN is not influenced by germ line variation of genes encoding signaling molecules in the GH/IGF-I axis, but suggests that such factors may affect the progression of dysplasic phenotype.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 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".