Abstract 5157: Prolactin plays a role in regulating fatty acid synthesis and metabolism in the prostate cancer cell line PC-3
Bibliographic record
Abstract
Abstract Introduction: Prostate cancer (PCa) metabolism is unique from other cancers due to a high reliance on fatty acid (FA) break down for energy. This phenomenon of FA dependence is exemplified clinically by poor tumor detection by PET scanning, which makes proteins involved in FA synthesis and metabolism interesting therapeutic targets in PCa. Two important proteins for fat metabolism are fatty acid synthase (FASN) and carnitine palmitoyl-transferase I (CPT1). FASN is responsible for de novo synthesis of long-chain (LC) FA and its activation is tightly regulated. CPT1 is a rate-limiting enzyme, which shuttles LC-FA into the mitochondria for beta-oxidation. The hormone prolactin (PRL) plays a role in the normal prostate by increasing energy metabolism and citrate production. The receptor for PRL (PRLR) has 5 isoforms, which are speculated to have different signaling capabilities. Our lab has shown the ability of PRL to increase CPT1A, but not FASN, mRNA and protein levels in human breast cancer cells. We hypothesized that PRL plays a similar role in PCa FA synthesis and metabolism due to the known presence of PRLR in these cells. The objectives of this study were to 1) identify which PRLR isoforms are expressed 2) determine if mRNA or protein levels of FASN and CPT1A change in response to PRL dosing and 3) establish if PRLR isoform expression plays a role in the results obtained in objective #2. Methods: PNT1A (normal prostate epithelial) and PC-3 (PCa) cells were dosed with 0, 50 or 100 ng/ml PRL. The mRNA levels for CPT1A and FASN were measured with RT-qPCR. For protein expression of FASN and CPT1A 30 ug of protein was loaded onto SDS-PAGE gels, followed by transfer to PVDF membranes, incubated in primary and then secondary antibodies and finally ECL reagent was added to the membranes for band detection. Over-expression studies were performed using lipofectamine 2000 to transiently over-express the long form or a shorter truncated version of the PRLR that were cloned into an expression vector. Over-expression studies were analyzed using Western blotting for FASN and CPT1A as mentioned above. Results: Both PNT1A and PC-3 cell lines express various PRLR isoforms. PRL did not have a significant effect on FASN or CPT1A mRNA levels in either cell type. Western blotting revealed significant changes for FASN and CPT1A protein levels in PC-3 cells at the 100 ng/ml dose. PRLR isoform over-expression studies indicated that isoform expression does appear to be an important variable in how PRL affects FASN and CPT1A protein levels. Conclusion: This project indicates a role for PRL in regulating FA synthesis and metabolism in the PCa cell line PC-3. Regulation at the protein level appears to be influenced by the PRLR isoform that is predominately expressed. These results suggest that PRL and/or its receptors could be a therapeutic target in treating prostate cancer. This project was supported by funding provided from CIHR to GS. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5157. doi:1538-7445.AM2012-5157
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".