Telomeres and peroxisome proliferator-activated receptor gamma in the development of human breast cancer
Bibliographic record
Abstract
Breast cancer is the most common internal malignancy afflicting North American women. The development of breast cancer involves a sequential progression through defined clinical and pathological stages beginning with normal epithelium and progressing to hyperplasia, ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and culminating in metastatic disease. This progression into metastatic disease is characterized by many molecular alterations, including the shortening of total telomere length. Cancer cells containing critically short telomeres activate telomerase to avoid cell death and it has been demonstrated to occur in 90% of breast carcinoma. Furthermore, telomerase activity has been shown to be modulated by ligands for peroxisome proliferator-activated receptor gamma (PPARγ). The integral role of telomeres in cancer progression has motivated extensive research into targeting telomeres for diagnosis and treatment of breast cancer. In the present study, the telomere shortening on chromosome 17q was analyzed in relation to average telomere length in normal epithelium, DCIS and IDC to determine if the shortening of specific telomeres can be used as a molecular marker for breast cancer progression. Furthermore, the effect of the PPARγ ligand troglitazone on telomerase activity and gene expression was examined in MDA-MB-231 breast cancer cells to determine if PPARγ ligands have an anti-telomerase effect. Results indicated that telomere shortening on chromosome 17q, harboring several genes involved in breast cancer development, is higher than the average shortening of all telomeres. Furthermore, troglitazone reduced telomerase activity in MDA-MB-231 cells independently of PPARγ activation. In addition, troglitazone inhibited cell proliferation and the cell cycle signaling pathway on MDA-MB-231 and MCF-7 breast cancer cell lines through different mechanisms. Results from microarray comparative genomic hybridization also indicated that the PPARγ gene is lost or deleted in 58% of clinical breast cancers. In conclusion, the high shortening of telomere on chromosome 17q suggests that telomere shortening is not a linear process and may serve as a marker for breast cancer progression. Furthermore, troglitazone demonstrated anti-telomerase and anti-proliferative activity in breast cancer cells. However, these effects vary depending on the cell type and experimental models employed. Finally, the loss of the PPARγ gene in over 50% of breast cancers indicates a potential tumor suppressor role for PPARγ in the development of breast cancer.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| 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".