Abstract 4599: The RING E3 ligase BCA2 is regulated by estrogen and co-expressed with estrogen receptor in breast cancer cells
Bibliographic record
Abstract
Abstract The Breast Cancer Associated gene 2 (BCA2) protein contains a RING H2 finger and a zinc finger near the N-terminus. The presence of the RING domain allows BCA2 to function as an E3 ligase. RING finger proteins play critical roles in mediating the transfer of ubiquitin and ubiquitin-like modifiers to substrates; such modifications are pivotal in regulating protein homeostasis and basic cellular processes such as gene-transcriptional regulation. The RING domain in BCA2 is known to act as an E3 ligase in its auto-regulation, and is suspected to play a role in the modification of other proteins. In a cohort of 945 primary invasive breast cancers examined for estrogen receptor-alpha (ER) and BCA2 expression, 67% were found to be ER-positive, 74% of which also exhibited strong nuclear BCA2 protein expression (p = 0.004). In this study, we examined potential mechanism(s) underlying BCA2 and ER co-expression at transcriptional and protein levels. Estrogen-responsive and non-responsive breast cancer cell lines were used as model systems. To investigate whether BCA2 is an estrogen responsive gene, BCA2 and ER-positive T47D breast cancer cells were cultured in medium containing charcoal-stripped fetal calf serum supplemented with 10 nM and 100 nM 17β-estradiol respectively over a 72-hour time course. Northern and Western blots showed a 17β-estradiol-associated induction of BCA2 mRNA and protein within 72 hrs. Moreover, when ER is ectopically or stably expressed in ER and BCA2-negative MDA-MB-231 cells, prominent BCA2 expression is detected, suggesting that ER is responsible for induction of BCA2 transcription. To investigate a possible interaction of BCA2 and ER at a transcriptional level, bioinformatic analysis of the BCA2 promoter region revealed ER and PR binding sites as well as possible sites of general transcription factors. Together our data indicates that BCA2 is upregulated in response to estrogen and that BCA2 expression can be rescued by the introduction of ER, suggesting that ER and BCA2 may be participating in crosstalk at the transcriptional level. Further investigations into this phenomenon are necessary to determine the possibility of the development of drugs targeting BCA2 in order to manipulate ER. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4599.
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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 | 0.001 |
| 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) | 0.004 | 0.002 |
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".