Abstract 83: Differential regulation of PTEN in ERα positive and negative ovarian cancer cells during cisplatin induced apoptosis
Bibliographic record
Abstract
Abstract The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor is a central negative regulator of the PI3K/AKT signaling cascade and suppresses cell survival as well as cell proliferation. PTEN is found to be either inactivated or mutated in various human malignancies. In the present study we have investigated the regulation of PTEN levels during cisplatin induced apoptosis in estrogen receptor alpha (ERα) positive (OVCAR-3 and SKOV-3) and negative (A2780 and A270-CP) ovarian cancer cell lines. Cells were treated with 10μM cisplatin for 24hrs. Transcript and protein levels were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting, respectively. The results showed that PTEN levels were significantly decreased in ERα-negative A2780 cells at both the transcript and protein levels; however, there was no change in PTEN levels in ERα-positive cells and cisplatin resistant cells (A2780-CP) in the presence of cisplatin. The decrease in PTEN was accompanied with an increase in the levels of Akt phosphorylation in A2780 cells. Cisplatin treatment induced the activation of caspase-3, -7, -8, -9 and cleavage of Parp in all the cell lines tested in the study except A2780-CP cells. In A2780 cells, restoration of PTEN levels was achieved upon pre-treatment with Z-VAD-fmk (caspase inhibitor) and not with MG132 (proteasome inhibitor), suggesting that, in addition to the regulation of PTEN at transcript level, caspases are also involved in the decrease of PTEN protein levels in A2780. The decrease in pro-apoptotic PTEN levels both at the transcriptional and post-translational levels and increase in survival factor pAkt in ERα-negative ovarian cancer cells suggest that cisplatin treatment could further exacerbates drug resistance in ERα-negative ovarian cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 83. doi:1538-7445.AM2012-83
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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) | 0.002 | 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".