Lack of Demonstrable Autocrine Hedgehog Signaling in Human Prostate Cancer Cell Lines
Bibliographic record
Abstract
PURPOSE: Several recent reports highlighted the role of hedgehog signaling in prostate cancer. However, the relative contributions of autocrine and paracrine hedgehog signaling to tumor growth and progression are unclear. Efforts to model autocrine signaling for drug development have been hampered by conflicting reports of the presence or absence of autocrine signaling in established human prostate cancer cell lines. MATERIALS AND METHODS: We comprehensively characterized the expression of hedgehog pathway genes in the 3 prostate cancer cell lines LNCaP, PC3 and 22RV1 (American Type Culture Collection, Manassas, Virginia). We also examined their response to Shh ligand and to the hedgehog pathway inhibitor cyclopamine (Toronto Research Chemicals, Toronto, Ontario, Canada). RESULTS: Expression of hedgehog ligand, patched and Gli1 in all 3 cell lines was lower than the expression level in normal human prostate tissue. All 3 cell lines showed hedgehog target gene activation when transfected with an activated form of Gli2 but none showed a detectable transcriptional response to hedgehog ligand or to transfection with an activated form of smoothened. Furthermore, treatment with the hedgehog pathway inhibitor cyclopamine did not inhibit hedgehog target gene expression in any of the 3 prostate cancer cell lines, although cyclopamine inhibited proliferation in culture. CONCLUSIONS: LNCaP, PC3 and 22RV1 show no evidence of autocrine signaling by ligand dependent mechanisms and cyclopamine mediated inhibition of growth in culture occurs without of any discernible effect on canonical hedgehog pathway activity.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".