Uterine cancer cells proliferate differently in response to 17β-estradiol in presence or absence of tamoxifen, raloxifen and ICI 182 780
Bibliographic record
Abstract
4020 Antiestrogens like tamoxifen, raloxifen and ICI 182 780 are medication for preventing and treating hormonodependant cancers such as breast cancers. However, long-term exposure to tamoxifen has been shown to induce endometrial cancers. The aim of this study was to determine the effect of 17β-estradiol in presence or absence of antiestrogens in human uterine cancer cells (HeLa, HEC-1-A, KLE, RL-95-2, Ishikawa et TOV-1078D) and to further investigate how they act at the intracellular level. Real-time RT-PCR and Western analyses were carried out to measure ERα and ERβ expressions. Total protein and RNA were extracted and the results indicated that ERβ is expressed in all cell lines but at different levels. The presence of ERα was detected only in Ishikawa cells at low level and was strongly expressed in TOV-1078D, a novel endometrial cancer cell line. 17β-estradiol induced cell proliferation at low dose in cell lines expressing ERα protein. Proliferation in most of the cell lines was reduced at high concentrations (10 -7 -10 -5 M) from 5-40% with 17β-estradiol, 20-75% with tamoxifen, 5-55% with raloxifen and 25-40% with ICI 182 780. Interestingly, in HEC-1-A cells, raloxifen and ICI 182 780 at high concentrations caused an increased of 180% and 110% of cell proliferation respectively. In experiment two, cells were treated with the same agents in a phenol red-free media containing 10% charcoal-dextran stripped FBS.Preliminary results in these conditions showed a significant and different effect of those factors. Cell proliferation of five cell lines was reduced (except KLE cells) by 50-70% in presence of 10 -6 M tamoxifen. However, at the same concentration raloxifen and ICI 182 780 had no effect on cell proliferation in the six cell lines. Because 17β-estradiol has been shown to act through the PI3-K/Akt pathway in many systems, we hypothesised that Akt might be involved in regulating this process. However, no significant fluctuations were observed in term of Akt activity/phosphorylation in response to antiestrogens. Further investigation are currently being carried out to confirm these observations and to explore other signalling pathways that might influence survival/death of endometrial cells in response to antiestrogens. Supported by CIHR (MOP-66987).
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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) | 0.002 | 0.001 |
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".