Effect of testosterone on the mitochondrial aspartate aminotransferase in prostate cancer cell lines
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 45, 2004 1940 Epidemiological and experimental studies have shown that long chain fatty acids (LCFA) and testosterone influence the development and subsequent progression of prostate cancer. One possible link between LCFA and testosterone might be through a mitochondrial matrix protein—mitochondrial aspartate aminotransferase (mAAT) and a protein located on the plasma membrane—fatty acid binding protein (FABPpm). mAAT plays a role in amino acid metabolism and is a critical component of the malate/aspartate shuttle. Cells uptake LCFA via the FABPpm. Comparison of chemical and immunological properties led to the discovery that mAAT is identical to FABPpm and is coded for by a single nuclear gene. The mechanism by which this mitochondrial protein is targeted to two different locations within the cell has yet to be elucidated. It has been determined that mAAT is regulated by testosterone only in prostate secretory epithelial cells, a site where prostate cancer initially develops. It is hypothesized that since mAAT is regulated by testosterone in the prostate, FABPpm may also be regulated by testosterone. With an increase in testosterone, there should be an increase in the levels of FABPpm followed by an increase in the uptake of LCFA. The cell lines chosen for this study were the androgen sensitive LNCaP and the androgen insensitive CL1, which were derived from LNCaP. A synthetic androgen, R1881, was used in substitution of testosterone. Immunofluorescence microscopy data show a difference in the staining pattern on the plasma membrane between LNCaP cells treated with 0.1nM R1881 versus control. Conversely, CL1 cells demonstrated no change in the staining pattern. Western blots verified the immunofluorescence data. In order to visualize and quantify these results, uptake studies using fluorescently labeled LCFA were done using real time confocal laser scanning microscopy and flow cytofluorimetric analysis. In conclusion, this data suggests that testosterone regulates the uptake of LCFA into prostate cancer cells. Significantly, LCFA play an important role in steroidogenesis implying there could be a continuous cycle of stimulation, where a steroid stimulates LCFA uptake while a LCFA stimulates steroidogenesis. (Supported by the Canadian Institute of Health Research (CIHR) to G.S.)
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".