Abstract 1719: Differential Mcl-1 processing in evasion of DCA-induced apoptosis of colorectal cancer cells.
Bibliographic record
Abstract
Abstract Recent evidence indicates that dichloroacetate (DCA) may be a cancer-specific agent that targets the unique metabolism of cancer cells, avoiding disruption of normal somatic cells. However, our laboratory has shown that some human colorectal cancer cell lines do not show the predicted response to DCA treatment, and the molecular mechanism responsible for this is currently unknown. Of interest is the Bcl-2 protein family, which consists of both pro- and anti-apoptotic members. The expression, regulation, and interactions of the Bcl-2 proteins will mediate the release of cytotoxic molecules such as cytochrome c from the mitochondria into the cytosol, activating apoptosis via a caspase cascade. Differential regulation of the Bcl-2 proteins in response to DCA treatment may indicate whether apoptosis will be induced in cancer cell lines. The human colorectal cancer cell line HCT116 was cultured and exposed to DCA as well as 5-fluorouracil, a known initiator of Bcl-2 protein-mediated apoptosis. Key changes in Bcl-2 protein expression were analyzed using immunoblotting. The expression of Mcl-1, an anti-apoptotic Bcl-2 protein, occurred at 40-kDa in all treatments, and at 28-kDa only in non-DCA treatments. PCR for the known splice variants of Mcl-1 confirmed only one gene product, suggesting the involvement of post-translational modification. The presence of cleaved caspase 3 indicates that an increase in 28-kDa Mcl-1 compared to 40-kDa Mcl-1 occurs with apoptosis in 5-fluorouracil treated cells, but does not occur in DCA-treated cells, which were not apoptotic. This suggests that Mcl-1 modification may be acting to modulate susceptibility to DCA treatment. The interactions involved in or resulting from these responses are currently under investigation. Using modified HCT116 cells without functional p53 or without functional Bax, the role of these two proteins will be emphasized. Co-immunoprecipitation of Mcl-1 will allow changes in its binding partners, such as p53, to be observed in response to DCA treatment. By utilizing mitochondrial and cytosolic fractions for protein analysis, the effect of DCA on mitochondrial localization of proteins such as Bax and the release of cytochrome c from the mitochondria will be observed. Further research may provide insight into the mechanism by which some human cancer cell lines are protected against DCA-induced cell death, and the potential role of a pathway involving Mcl-1 in this cell-specific protection. Citation Format: Leanne M. Delaney, Brenda L. Coomber. Differential Mcl-1 processing in evasion of DCA-induced apoptosis of colorectal cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1719. doi:10.1158/1538-7445.AM2013-1719
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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 | 0.001 |
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".