Abstract 1018: Role of Stat3 vs Stat5 in the differentiation of HC11, mouse breast epithelial cells
Bibliographic record
Abstract
Abstract The Signal Transducer and Activator of Transcription (Stat)3 and Stat5 are transcription factors involved in normal breast development, and are hyperactivated in 30-50% of breast cancers. Stat5 is required for breast epithelial cell differentiation and is over-expressed in breast cancers with a more differentiated phenotype. On the other hand, constitutive over-activation of Stat3 can drive expression of genes involved in survival, migration and angiogenesis, while mutationally activated Stat3 (Stat3C) can transform cultured cells, indicating that Stat3 may play an important role in cancer etiology. Following activation of a number of growth factor or cytokine receptors such as interleukin-6 or expression of oncogenes such as Src, Stat3 is phosphorylated at tyr-705, dimerizes and migrates to the nucleus where it activates transcription from a number of genes involved in cell division and survival, such as survivin, Bcl-xL, Mcl1 and myc, while it downregulates expresssion of the tumor suppressor p53. We recently discovered a novel pathway of activation of Stat3: Engagement of cadherins (E-, N-cadherin or cadherin-11), cell to cell adhesion proteins induces a dramatic increase in the levels of the Rac1 and Cdc42 small GTPases, and this leads to interleukin-6 transcription, hence Stat3 activation. The differentiation of HC11, nonneoplastic mouse breast epithelial cells requires prolactin, hydrocortisone and insulin, added at confluence. Since confluence activates Stat3, we examined the role of Stat3 upon breast epithelial cell differentiation, measured by cellular morphology and expression of the milk proteins, β-casein or whey acidic protein. Through pharmacological inhibition with CPA7 or S3I-201, our results demonstrate that Stat3 is, in fact, required for HC11 cell differentiation. In contrast, constitutive expression of mutationally activated Rac1 was found to block differentiation while inducing transformation. In sharp contrast, our results indicate that Stat5 is upregulated by the differentiation cocktail but is unaffected by cell density, while expression of activated Stat5 promotes a more differentiated phenotype. Taken together, our results demonstrate that Stat3 and Stat5 may constitute independent prognostic markers as well as treatment targets for breast cancer. Citation Format: Jamaica Cass, Maximilian Niit, Rozanne Arulanandam, Bruce Elliott, Leda Raptis. Role of Stat3 vs Stat5 in the differentiation of HC11, mouse breast epithelial cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1018. doi:10.1158/1538-7445.AM2015-1018
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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 | 0.001 |
| 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".