Hypomethylation of urokinase (uPA) promoter in hormone-dependent malignancies : prognostic and therapeutic implications
Bibliographic record
Abstract
Urokinase plasminogen activator (uPA) promotes tumor invasion and metastasis in several malignancies including breast and prostate cancer. High levels of uPA are associated with invasive and metastatic characteristics of cancer. I examined the differential regulation of uPA expression by DNA methylation in normal, hormone responsive and hormone insensitive human breast and prostate cancer cell lines. Lack of uPA expression in normal and hormone responsive cells is due to methylation of uPA promoter. Treatment of these cells with a demethylating agent resulted in induction of uPA, higher invasive capacity of the cells, and significant increase in tumor volume. These studies demonstrated that DNA methylation is the molecular mechanism responsible for uPA gene silencing in normal and hormone responsive cancer cells. Since levels of uPA production is already a reliable prognostic marker of disease progression, determination of uPA promoter methylation status can potentially serve as a reliable early marker for induction of uPA and thus progression of cancer into metastatic stages. I therefore examined the methylation status of uPA promoter in surgical biopsy samples from patients with breast cancer of different grades and found that hypomethylation of uPA promoter is in fact associated with induction of uPA expression and poor grade in these patients. Determination of uPA promoter methylation status can therefore serve as an early reliable indicator of uPA production in breast cancer patients. Since uPA expression and its hypomethylated state is strongly correlated with the malignant phenotype, I utilized uPA gene in the highly invasive human breast cancer cells as a model system to test the hypothesis that pharmacological reversal of the uPA hypomethylation can result in its silencing and inhibition of metastasis. I found that treatment of these cells with the methylating agent SAM significantly inhibits uPA expression, tumor cell invasion, t
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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 | 0.000 |
| 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 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".