Pharmacological Inhibition of DNA Methylation Induces Proinvasive and Prometastatic Genes In Vitro and In Vivo
Why this work is in the frame
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Bibliographic record
Abstract
The mechanism of action of DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR), a potential anticancer agent is believed to be activated by the demethylation of tumor suppressor genes. We tested here the hypothesis that demethylating agents also demethylate and activate genes involved in invasion and metastasis and therefore might increase the risk of developing tumor metastasis. The effect of 5-aza-CdR on noninvasive human breast cancer cells MCF-7 and ZR-75-1 was evaluated by cell proliferation, invasion, and migration assay. The ability of 5-aza-CdR to activate a panel of silenced prometastatic and tumor suppressor genes was evaluated using reverse transcription-polymerase chain reaction and bisulfite DNA sequence analysis in vitro and for change in tumor growth and gene expression in vivo. Treatment of MCF-7 and ZR-75-1 with 5-aza-CdR diminished cell proliferation, induced tumor suppressor RASSF1A, and altered cell cycle kinetics' G(2)/M-phase cell cycle arrest. While these effects of 5-aza-CdR slowed the growth of tumors in nude mice, it also induced a battery of prometastatic genes, namely, uPA, CXCR4, HEPARANASE, SYNUCLEIN gamma, and transforming growth factor-beta (TGF-beta), by demethylation of their promoters. These results draw attention to the critical role of demethylation as a potential mechanism that can promote the development and progression of tumor metastasis after demethylation therapy as an anticancer treatment.
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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