Epithelial phosphatase and tensin homolog regulates intestinal architecture and secretory cell commitment and acts as a modifier gene in neoplasia
Bibliographic record
Abstract
ABSTRACT Phosphatase and tensin homolog (PTEN) , a negative regulator of the phosphatidylinositol 3‐kinase/Akt pathway, is one of the most frequently mutated/deleted tumor suppressor genes in human cancers. The aim of this study was to gain insight into the role played by PTEN in intestinal homeostasis and epithelial cell function. Using the Cre/loxP system, we have generated a mouse with a conditional intestinal epithelial Pten deficiency. Pten mutant mice and controls were sacrificed for histology, immunofluorescence, Western blot, and quantitative polymerase chain reaction analysis. Our results show that loss of epithelial Pten leads to an intestinalomegaly associated with an increase in epithelial cell proliferation. Histological analysis demonstrated significant perturbation of the crypt‐villus architecture, a marked increase in goblet cells and a decrease in enteroendocrine cells, suggesting a role for Pten in the commitment of the multipotential‐secretory precursor cell. Loss of epithelial Pten does not result in induction of nuclear β‐catenin protein levels, nor is it sufficient to promote tumorigenesis initiation. However, it severely enhances intestinal tumor load in Apc Min/+ mice, in which c‐Myc is already deregulated. These results reveal an unknown function for Pten signaling in the commitment of multipotential‐secretory progenitor cells and suggest that epithelial Pten functions as a modifier gene in intestinal neoplasia.—Langlois, M.‐J., Roy, S. A. B., Auclair, B. A., Jones, C., Boudreau, F., Carrier, J. C., Rivard, N., Perreault, N. Epithelial phosphatase and tensin homolog regulates intestinal architecture and secretory cell commitment and acts as a modifier gene in neoplasia. FASEB J. 23, 1835–1844 (2009)
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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 | 0.000 | 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) | 0.000 | 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".