Abstract 1448: Investigating the effects of estrogen on the initiation of prostate cancer
Bibliographic record
Abstract
Abstract Background: Prostate cancer (PCa) is responsible for ~10% of cancer-related deaths in men. Nkx3.1 is an androgen-regulated gene expressed primarily in the prostate, which encodes a tumor suppressor protein important for male reproductive development. Loss of nkx3.1 is thought to lead to prostatic intraepithelial neoplasia (PIN), the pre-invasive form of prostatic adenocarcinoma. Previous evidence suggests that estrogenic dysregulation and testosterone imbalance play a significant role in PCa initiation and progression. Objectives/Aims: We aimed to investigate how estrogen impacts the progression of PIN in the anterior prostate of mice lacking nkx3.1. Methods: To investigate the effect of long-term exposure to 17β-estradiol (E2), nkx3.1+/+ and nkx3.1−/− 12-week-old mice were given 2 mg/day of E2 over 90 days by subdermal implantation of 90-day extended-release tablets. After 90 days, the anterior prostate lobes of the mice were harvested and analyzed post-treatment for signs of pre-cancerous tissue. The immediate, early effect of E2 exposure was also investigated by the subcutaneous injection of 8- and 20-week-old mice with 0.300 mg/kg of E2. Within two hours, the anterior prostate lobes were harvested, and ~500 ng/μL of RNA was isolated from the tissues. cDNA was reverse-transcribed, in triplicate, from the RNA and the expression of c-myc, p53, estrogen receptor ERα (ESR1), and ERβ (ESR2) were assessed via qRT-PCR. Three technical replicates from three biological replicates were performed for each treatment. Results: Nkx3.1−/− mice chronically exposed to elevated E2 developed PIN following E2 treatment, while the placebo group had tissue hyperplasia. Nkx3.1+/+ mice had normal prostate tissue regardless of E2 treatment. In response to immediate exposure to E2, the prostates of 8-week-old nkx3.1+/+ mice showed reduced c-myc expression. 8-week-old nkx3.1−/− mice showed no changes in expression of any of the four genes assayed, in response to E2 as compared to the placebo treatment. In contrast, regardless of exposure to E2, c-myc, p53, and ESR2 were significantly elevated in these mice compared to the nkx3.1+/+ groups. Furthermore, c-myc and p53 expression was suppressed in 20-week-old nkx3.1−/− mice in response to E2, while ESR1 and ESR2 remained unchanged. Conclusion: Our evidence suggested that prolonged exposure of wild-type mice to E2 had no pathohistological impact on the anterior prostate tissue. In nkx3.1-deficient mice, however, E2 exposure promoted the onset of PIN, and caused immediate differential expression of estrogen-responsive genes, suggesting a role of nkx3.1 in protecting the prostate in the presence of a hormonal imbalance. Citation Format: Nash S. Denic, Ashlyn Swift-Gallant, Kenneth R. Kao. Investigating the effects of estrogen on the initiation of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1448.
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.
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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".