Activation of the Canonical <scp>WNT</scp> Signaling Pathway Promotes Ovarian Surface Epithelial Proliferation Without Inducing β‐Catenin/Tcf‐Mediated Reporter Expression
Bibliographic record
Abstract
BACKGROUND: In response to activation of the canonical WNT signaling pathway, β-catenin cooperates with Lef/Tcf (lymphoid enhancer factor/T-cell factor) transcription factors to drive expression of Wnt target genes. The canonical WNT signaling pathway is involved in development, wound repair, and tumorigenesis. Studies examining the involvement of the canonical WNT signaling pathway in the development of ovarian surface epithelium (OSE) and ovarian carcinogenesis, however, have recently begun to emerge. In this study, we investigated the modulation of β-catenin and β-catenin/Tcf-signaling activity within the OSE using responsive transgenic mice and examined the response of primary OSE cells and ovarian cancer cell lines to activation of the canonical WNT signaling pathway. RESULTS: β-catenin was localized to the lateral membrane of the ovarian epithelium. Stimulation of primary OSE cells in vitro with LiCl or Wnt3a led to GSK-3β inhibition and stabilization of β-catenin but failed to induce β-catenin/Tcf-mediated lacZ expression. Furthermore, E-cadherin expression was downregulated and the proliferative potency of OSE cells increased. Of four ovarian cancers cell lines screened, only the HEY cell line demonstrated induction of luciferase reporter upon canonical WNT stimulation. CONCLUSIONS: These observations suggest that in ovarian adenocarcinoma, dysregulated WNT signaling may not always be indicative of β-catenin/Tcf-mediated transcriptional activity.
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How this classification was reachedexpand
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 | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".