Differential Regulation of Clusterin and Its Isoforms by Androgens in Prostate Cells
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Clusterin mRNA levels were shown to increase dramatically in rat ventral prostate following castration, and clusterin was therefore originally thought to be repressed by androgens. It was later discovered that the increased clusterin levels are most likely due to castration-induced apoptosis of the prostatic epithelium rather than direct action of the androgen receptor (AR). In the studies presented here, LNCaP cells in culture and rat prostate organ culture were treated with androgens. Clusterin mRNA and protein are shown to increase with androgen treatment in a time- and dose-dependent manner. This induction of clusterin requires AR and can be inhibited by casodex, an AR antagonist. We have found that the first intron of the clusterin gene contains putative androgen response elements. The intronic region is shown to be bound by AR in chromatin immunoprecipitation assays and is transactivated by AR in reporter assays. Two isoforms of clusterin result from alternate transcriptional start sites. Both isoforms are cytoprotective; however, Isoform 1 has the capacity to produce a splice variant that is apoptotic. Real time PCR was used to determine the response of the two isoforms to androgens. Intriguingly, these results illustrated that Isoform 2 was up-regulated, whereas Isoform 1 was down-regulated by androgens. Isoform 2 was also increased as the LNCaP xenograft tumor progressed to androgen-independence, whereas Isoform 1 was unaltered. This androgen regulation of clusterin may underline the cytoprotective role of androgens in normal prostate physiology as well as play an antiapoptotic role in prostate cancer progression.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 it