Role of cyclooxygenase-2 and fatty acid synthase in breast cancer development
Bibliographic record
Abstract
Cyclooxygenase-2 (COX-2) and fatty acid synthase (FAS) are over-expressed in breast cancer. Inhibitors of COX-2 and FAS decrease proliferation and induce apoptosis in breast cancer cells. A previous study showed that the COX-2 inhibitor celecoxib not only inhibited rat mammary carcinogenesis, but also decreased fat deposition in rats fed a high fat diet, suggesting that celecoxib may affect lipid metabolism. We demonstrated that celecoxib suppresses FAS expression, and decreases fat accumulation by down-regulating c-Jun N-terminal kinase 1 (JNK1) in rats fed a high fat diet rich in n-6 polyunsaturated fatty acids (PUFAs). This finding suggests that not only inhibition of COX-2 but also down-regulation of FAS contribute to the chemopreventive effect of celecoxib. This observation led us to investigate the roles of both COX-2 and FAS in breast cancer development. We showed that COX-2 over-expression in breast epithelial cells inhibits proliferation, detachment-induced apoptosis and differentiation, and causes epithelial to mesenchymal transition (EMT). This finding suggests that COX-2 over-expression disturbs the homeostatic status of mammary epithelial cells, leading to partial transformation of these cells, and predisposing the mammary gland to tumorigenesis. Malignant transformation of breast epithelial cells is associated with elevated expression of FAS. We showed that inhibition of FAS by triclosan suppresses rat mammary tumorigenesis induced by N-methyl-N-nitrosourea (MNU). This finding suggests that FAS is a promising molecular target for breast cancer prevention. In cancers, de novo fatty acid synthesis is functionally linked to cell proliferation by providing fatty acids for the biosynthesis of cellular membranes, but the molecular link between these two processes was not known. We demonstrated that Sp1 coordinately regulates the expression of FAS, a key enzyme of fatty acid synthesis, and CDC25A, a key cell cycle protein, in estrogen-sensitive breast cancer cells. Thus, Sp1 is a molecular link between de novo lipogenesis and proliferation in these cells. Overall, findings of this thesis contribute to our knowledge relating to how COX-2 and FAS act to facilitate breast cancer development, and provide evidence that these enzymes could be potential targets for breast cancer prevention.
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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 | 0.001 | 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".