Emergence of Androgen Independence at Early Stages of Prostate Cancer Progression in <i>Nkx3.1; Pten</i> Mice
Bibliographic record
Abstract
Although androgen deprivation therapy is a widely used treatment for patients with advanced prostate cancer, it ultimately results in the emergence of a hormone-refractory disease that is invariably fatal. To provide insights into the genesis of this disease, we have employed an in vivo model to investigate how and when prostate epithelial cells can acquire the ability to survive and proliferate in the absence of androgens. In particular, we have been studying the evolution of androgen independence in Nkx3.1; Pten mutant mice, which develop prostatic intraepithelial neoplasia and adenocarcinoma as a consequence of aging, as well as androgen-independent phenotypes following castration. We now find that the prostate epithelial cells from these Nkx3.1; Pten mutant mice are capable of surviving and proliferating in the absence of androgens and that they develop androgen-independent phenotypes well before they display overt prostatic intraepithelial neoplasia or cancer phenotypes. Our findings in this mouse model show that acquisition of androgen independence can be uncoupled from overt cancer progression and raise the possibility that hormone-refractory disease can arise at early stages of prostate carcinogenesis.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".