The CAMA-1 breast cancer cell line as a model to investigate the role of environmental anti-androgens in breast carcinogenesis.
Bibliographic record
Abstract
2503 Exposure to environmental compounds that can alter sex-hormone signalling pathways may represent a risk factor for breast cancer. We recently reported that 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p’-DDE), the main metabolite of the insecticide DDT and a potent androgen receptor antagonist, was associated with tumor aggressiveness in women diagnosed with breast cancer. Since androgens have been shown to inhibit the growth of estrogen-responsive breast cancer cell lines, we tested the hypothesis that p,p’-DDE might block this growth inhibitory effect in CAMA-1 cells, a breast cancer cell line exhibiting high levels of estrogen and androgen receptors. CAMA-1 cell proliferation was determined by seeding 2 X 103 cells/well into 96 well plates and exposing them during 9 days to either 17β-estradiol (E2), dihydrotestosterone (DHT) or p,p’-DDE, alone or as binary or tertiary combinations, with cell culture medium changed every 3 days. After treatment, plates were frozen at -80°C and cell proliferation was subsequently determined by measuring DNA concentration in wells using the Cyquant® test. The maximum proliferative response of CAMA-1 cells was observed with 100 pM E2. DHT added alone to the cell culture medium did not increase cell proliferation, but concentrations of 100 and 500 pM DHT, in combination with 100 pM E2, reduced E2-induced proliferative response by 30% and 50%, respectively. p,p’-DDE alone had no effect on CAMA-1 cell growth. However, in combination with 100 pM E2 and 100 pM DHT, increasing concentrations of p,p’-DDE in the incubation medium (0.1 to 2.0 μM) restored the proliferative response induced by E2. A second series of experiments was conducted using the classic androgen receptor antagonist hydroxyflutamide (HF) instead of p,p’-DDE. HF was as potent as p,p’-DDE in restoring CAMA-1 cell growth in the presence of E2 and DHT. These results add biological plausibility to our previous epidemiological observations linking p,p’-DDE body burden to breast cancer aggressiveness. Moreover, CAMA-1 cells incubated with physiological concentrations of E2 and DHT constitutes a useful and simple model for in vitro screening of anti-androgenic compounds that can favour breast cancer progression. Additional experiments are underway to further delineate the mechanism of action involved by measuring the expression of genes controlled by sex-hormone signalling pathways in the CAMA-1 cell line.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.003 |
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".