The role of BIRC6, a member of the inhibitor of apoptosis protein (IAP) family, in the survival of human prostate cancer cells
Bibliographic record
Abstract
Prostate cancer is the most commonly diagnosed cancer and third leading cause of cancer deaths in Canadian men. Prostate cancers typically begin as androgen-dependent tumours susceptible to growth arrest/apoptosis induced by ablation of androgens. Although initially effective, androgen ablation frequently leads to the development of castration-resistant (androgen-independent) prostate cancer, which is generally also resistant to other available treatments. Development of castration-resistant prostate cancer is characteristically associated with marked increases in resistance to apoptosis. BIRC6 is a member of the Inhibitors of Apoptosis Protein (IAP) family which protects a variety of cancer cell lines from apoptosis. In the present study, we have investigated whether BIRC6 plays a role in prostate cancer and could potentially be useful as a novel therapeutic target. Analysis of a variety of human prostate cancer cell lines and clinical specimens for BIRC6 protein expression, using Western blot and immunohistochemical analyses, respectively, showed that BIRC6 protein is markedly expressed by the prostate cancer cell lines and by clinical cancer specimens, as distinct from benign prostate cells/tissue. In addition, analysis of the clinical specimens showed that elevated BIRC6 protein expression was found to be particularly associated with cancers of Gleason score 6-8 and with the development of castration-resistant disease. Specific, siRNA-induced reduction of BIRC6 expression in LNCaP cells led to a marked reduction in cell proliferation, associated with an increase in apoptosis markers and a decrease in autophagosome markers, indicating that BIRC6 plays a major protective role in the proliferation of LNCaP cells by inhibiting apoptosis and perhaps by enhancing autophagy. Taken together, the data suggest an important role for BIRC6 in prostate cancer growth and progression, particularly, in the development of treatment resistance. In conclusion, this study indicates - for the first time - that the BIRC6 gene and its product are potentially valuable targets for therapy of human prostate cancers. BIRC6-targeting drugs may be especially useful for sensitization of cancer cells in combination therapy.
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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) | 0.001 | 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".