Abstract 1035: Bcl2 is regulated by PKC and Akt and is associated with resistance to cisplatin in endometrial cancer cells.
Bibliographic record
Abstract
Abstract Endometrial carcinomas often show resistance to cisplatin. Bcl2 has been shown to be associated with cisplatin resistance in different types of cancers. However, there is no information concerning its possible involvement in chemoresistance and its regulation in endometrial carcinomas. We have tested the ability of cisplatin to induce apoptosis in KLE, a resistant endometrial carcinoma cell line, and examined the putative role for Bcl2 in regulating drug sensitivity. We have investigated the impact of cisplatin treatment on Bcl2 family members and Xiap, an inhibitor of caspase activity. Cisplatin treatment upregulated Bcl2 protein expression in a time-dependant manner in KLE cells, but had no significant impact on the levels of Bax, Bcl-xL and Xiap proteins. As demonstrated by RT-PCR, Bcl2 mRNA was not upregulated in response to cisplatin, suggesting that cisplatin act on Bcl2 expression through a post-translational mechanism. In KLE cells, Bcl2 inhibition by HA14-1 led to increased apoptosis induced by cisplatin. It has been shown that Akt, MAPK and PKC pathways are involved in the regulation of Bcl2 under various conditions and in different cell types. Therefore, KLE cells were treated with inhibitors of MAPK (PD98059) and PKC (CalphostinC) prior to cisplatin treatment. Inhibition of PKC prevented cisplatin-dependant upregulation of Bcl2 protein, while MAPK inhibition had no impact. We previously showed that KLE cell line express high levels of phosphorylated Akt (pAkt) isoforms. Then, KLE cells stably expressing shRNA for all three Akt isoforms were established. Treatment of these cells with cisplatin prevented the increase of Bcl2 expression and led to increased apoptosis by cisplatin. These data suggest a role for Bcl2 in cisplatin resistance in endometrial carcinoma cells. Also, they indicate that PKC and Akt are involved in regulation of Bcl2 expression in this experimental model. 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 1035.
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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) | 0.003 | 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".