Transcriptional Regulation Of The Threshold Response Of Prostate Cancer Cells To The Anti‐Androgen Casodex
Bibliographic record
Abstract
The anti‐androgen Casodex competes with the active metabolite of testosterone, 5α‐dihydrotestosterone (5 α‐DHT), for binding to the androgen receptor (AR) and blocks normal AR‐dependent signaling. In p53+/+/AR+ LNCaP and PC‐346C cell lines 50 or 100μM Casodex induce G1/G0 phase arrest as demonstrated by flow cytometry using propidium iodide. At higher doses casodex also induces apoptosis as measured by Apo‐BrdU incorporation. These data indicate that both LNCaP and PC‐346C cells display similar sensitivity and responses to Casodex treatment, and that the threshold concentration of Casodex required to induce apoptosis in these cells is between 50 and 100μM. Western analysis and immunohistochemistry demonstrate that Casodex induces a dose related decrease in nuclear AR levels and a concomitant increase in p53expression in both cell lines. RT‐PCR analysis reveals that at 50 μM Casodex the expression of p53 target genes responsible for G1/S transition including E2F and CDC2 are down‐regulated, while p21 transcription is up‐regulated. At 100 μM Casodex, the transcription of several pro‐apoptotic genes (including p21B and Bnip3L) is upregulated while the expression of survival genes including birc5 (survivin) is substantially downregulated. These observations suggest that at doses below the threshold for apoptosis Casodex only induces cell cycle arrest while at doses above the threshold the ani‐androgen induces transcription of pro‐apoptotic genes. This may have significant implications in the development of adjuvant therapies for prostate cancer. (Supported by the Coleman Foundation and Errant Gene Therapeutics)
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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 | 0.000 |
| 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) | 0.002 | 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 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".