Abstract B29: Ovarian hormones regulate C/EBPD induced EMT/MET transition in the human fallopian tube epithelia
Bibliographic record
Abstract
Abstract Introduction: The histologically normal BRCA1 mutation carrier fallopian tube epithelia (FTE), compared to controls, showed that CEBPD was upregulated in the luteal phase of the ovulatory cycle. CEBPD is involved with the maintenance of genomic stability, promoting cellular differentiation, and regulating the cell cycle in response to cytotoxic stressors. In breast epithelial cells, CEBPD protein expression correlated with estrogen receptor (ER) and progesterone receptor (PR) and was found to be associated with increased progression-free survival in breast cancer patients. In fallopian tube epithelia (FTE), CEBPD was also found to modulate the epithelial-to-mesenchymal (EMT)/mesenchymal-to-epithelial transition (MET) by modulating target genes of this pathway. Given the hormonal response of this gene and its function in modulating an EMT/MET, the objective of this study was to determine whether sex hormones influence CEBPD regulation of EMT/MET in the fallopian tube and thus ovarian cancer. Methods: Fresh fallopian tube (FTE) tissues were obtained from patients approved for collection by IRB. Immunohistochemical profiling on normal fallopian tube tissue and HGSC was performed using CEBPD, ER, and PR protein markers. FTE cell lines with a p53 mutation (R175H) were subjected to estradiol (50nM and 100nM) and 4-hydroxytamoxifen (10nM) and assayed using qRT-PCR and PCR. ANOVA and t-tests were conducted in GraphPad Prism software with significance set at p<0.05. Results: E-cadherin in normal fallopian tube tissue was highly expressed in both the luteal and follicular phase whereas vimentin was highly expressed in the follicular phase but showed a range of expression (low expression to high expression) in the luteal phase. CEBPD overexpression increased SNAIL expression (p<0.0001), consistent with previous findings; treatment with 50nM estradiol (E2) resulted in increased SNAIL and SLUG mRNA expression in FTE cell lines overexpressing CEBPD (p<0.0001) relative to controls and decreased ZEB1 and ZEB2 mRNA expression. Addition of tamoxifen to cells overexpressing CEBPD increased SNAIL mRNA expression compared to cells without tamoxifen (p<0.0001); however, a combination of both tamoxifen and estradiol added to these cells decreased SNAIL expression relative to controls. IL6 mRNA expression level was increased in CEBPD overexpressing cells compared to controls (p<0.0001), which was further increased by E2 (p<0.0001). Conclusion: Together these results demonstrate a role for CEBPD in modulating EMT/MET in normal FTE in a hormonally regulated manner, which during cancer formation and spread is critical for anoikis and metastasis. Furthermore, these data will facilitate an understanding of the early events of carcinogenesis in fallopian tube epithelia. Citation Format: Ramlogan Sowamber, Leah V. Dodds, Patricia Shaw, Sophia H.L. George. Ovarian hormones regulate C/EBPD induced EMT/MET transition in the human fallopian tube epithelia [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B29.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".