Constitutive activation of gp130 leads to neuroendocrine differentiation in vitro and in vivo
Bibliographic record
Abstract
BACKGROUND: Neuroendocrine (NE) differentiation in prostate tumors has been correlated with androgen independent disease and increased risk of death. In vitro, IL-6 initiates NE differentiation utilizing the signal transduction initiated by the interaction with IL-6R alpha and gp130. In this study we analysed the NE differentiation process in vitro and in vivo using the LNCaP androgen dependent cell line via ligand independent induction of NE differentiation. METHODS: LNCaP cells were transfected with a constitutively active gp130 subunit, gp130act. Cell proliferation rate was determined and clones were examined for neuroendocrine differentiation by morphological change, upregulation of CgA and serotonin and formation of dense core vesicles with LNCaP parental cells as the control. Xenograft formation was examined and compared in immunocompromised mice. RESULTS: Gp130act expression promoted significant neuroendocrine differentiation in vitro as determined by a NE like morphology change (increased neurite like extension formation), elevated CgA expression and the formation of dense core vesicles (DCV). These measures concurred with those examined in LNCaP cells following 100 ng/ml IL-6 treatment. Further investigation of the LNCaP gp130act cells in vivo, in immunocompromised androgen intact mice, confirmed that the NE like morphology, as determined by histological and high resolution transmission electron microscopy, was maintained. CONCLUSIONS: NE differentiation was initiated by the expression of gp130act in a ligand independent manner, highlighting the importance of gp130 in the neuroendocrine differentiation process. Further investigation of upregulated/downregulated gene expression in these cells may provide valuable insight into the NE differentiation process.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".