Oncogenic pathways in breast cancer downstream of Pten
Bibliographic record
Abstract
3987 The tumor suppressor protein Pten is commonly inactivated in human malignancies, including breast cancer. Pten has lipid phosphatase activity that antagonizes the function of PI3K and affects the PKB pathway. Comparative studies on breast cancer mouse models, MMTV-Wnt1 and MMTV-neu tumors show induction of both cyclinD1 and D2 in MMTV-Wnt1 tumors, but not in MMTV-neu tumors (Yu et al., Nature, 2001). Accordingly, MMTV-Wnt1, but not MMTV-neu tumor development is independent of cyclinD1. Li et. al. (2003) has shown that MMTV-Wnt1 tumors consists of both myo- and luminal- epithelial cells. These tumors also exhibit an expansion of Sca-1 and keratin 6 positive cell population suggesting stem cell origins of these tumors. On the other hand, MMTV-neu tumors do not possess these properties. To elucidate the oncogenic pathways downstream of Pten in breast cancer and the role of D-type cyclins in cancer progression, We are analyzing mouse mammary tumors in conditionally knock-out Wap-Cre:Ptenf/f mice. Preliminary data suggest that both cyclinD1 and D2 are induced in some of the Pten mutant tumors. To further elucidate the importance of cyclinD1 in tumor initiation and progression downstream of Pten, Wap-Cre:Ptenf/f mice were crossed with CyclinD1 -/- mice to generate Wap-Cre:Ptenf/f:CyclinD1 -/- mice; incidence of tumor is monitored. Histological analyses revealed that mutations in Pten give rise to at least two types of tumors: adenocarcinoma and adenosarcoma. Immunostaining of these tumors show the presence of both myo- and luminal epithelial cells and keratin6 positive cells in a fraction of these tumors. FACS analyses of Pten tumors also suggest an expansion of Sca-1 positive cells compared to mammary gland from virgin or pregnant mice. These observations suggest that aberrant signaling of Pten may induce at least two distinct oncogenic pathways, one of which like MMTV-Wnt1 tumors, may target the stem cell population and the other pathway, like MMTV-neu tumors, may targets more committed progenitor cells. To further analyze oncogenic pathways downstream of Pten, we have generated tumorspheres from Pten mutant tumors. These tumourspheres can be propagated in ultra-low attachment plates in DMEM/F12 media supplemented with EGF, FGF and B-27. These tumorspheres express both luminal and myo-epithelial cell markers when plated on collagen-coated slides. Understanding Pten-dependent tumor initiation may open new avenues for therapeutic interventions for breast cancer treatment.
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".