Abstract LB-51: Pten null prostate tumorigenesis and prostate stem cell activity are inhibited by targeted knockout of the Survivin gene
Bibliographic record
Abstract
Abstract Survivin, a member of the inhibitor of apoptosis family, is highly expressed in various cancers including prostate cancer. In the conditional Pten deletion mouse model, we showed a correlation between increased levels of survivin with the growth of the prostate tumor (Cancer Res. 66: 4285–90, 2006), and more recently described that high levels of survivin might also be associated with the cancer stem cells of this model (Cancer Res. 70: 7294–303, 2010). Here we report that homozygous deletion of the Survivin gene specifically in mouse prostate epithelium suppresses prostate tumorigenesis without affecting postnatal prostate development and growth. Mouse prostates with double conditional knockout of Survivin and Pten that were collected at 8.5 weeks of age appear to exhibit normal gross morphology, histology and cytology, in contrast to the detection of hyperplasia, dysplasia and prostatic intraepithelial neoplasia (PIN) lesions in mouse prostates with bi-allelic Pten inactivation. While the mice with Pten deletion alone uniformly develop numerous invasive adenocarcinoma lesions in all of the prostate lobes by 17–20 weeks of age, our analysis to date of a single double knockout animal at 17 weeks reveals mostly PIN lesions in the anterior and the ventral prostate lobes with the dorsolateral lobe exhibiting detectable foci of adenocarcinoma. As the animals age, increased number of animals at this age and other advancing age groups remain to be evaluated for the significance of this observation and the possibility that the isolated lesions detected in the double knockout might be related to incomplete recombination in Survivin alleles in the target cells remains to be tested. In general, we observe a dramatic reduction in the proliferation index, as assessed by Ki67 staining, in the prostate tissue with the double deletion of Pten and Survivin compared to Pten deletion alone. We propose that survival of the proliferating abnormal cells is compromised by the intracellular loss of survivin. We used adenovirus-Cre to knock-out Survivin in stem cell fractions isolated from the prostate of the normal mouse with floxed Survivin alleles. It is very interesting to find that loss of survivin significantly lowers in vitro proliferation, spheroid-forming capability and survival potential of these cells, implicating a strong cytoprotective role of survivin for the prostate stem cells. Thus, it would now be important to extend the study for evaluation of the function of survivin in the prostate cancer stem cells, a compartment that may indeed be critical to the process of prostate tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-51. doi:10.1158/1538-7445.AM2011-LB-51
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".