Abstract 1096: Prostate tumor growth in pbARR2-Cre PTEN knockout mice is delayed in GH/IGF-I deficient mice
Bibliographic record
Abstract
Abstract Growth hormone/insulin-like growth factor I (GH/IGF-I) axis has been related to risk of prostate cancer (PCa). We have previously reported that androgen-responsive, castration-resistant (CR), and androgen-independent (AI) PCa xenografts develop more slowly in little murine hosts. The little (lit/lit) phenotype is due to a D60G missense mutation in the GH-releasing hormone receptor (GHRHR) resulting in loss of pituitary GHRHR function and suppression of GH and IGF-I expression. PTEN is a tumor suppressor gene that is frequently mutated in a variety of spontaneous cancers, including PCa. The prostate-conditional PTEN-null mouse represents the first animal model in which deletion of a single endogenous gene leads to invasive PCa. To investigate the role of GH/IGF-I axis on in vivo prostate carcinogenesis and neoplastic progression, we crossed pbARR2-Cre, PTEN(fl/fl) mice (PTEN-/-) with IGF-I deficient lit mice, and produced lit/lit and lit/+ PTEN-/- mice. To complement the in vivo experiments, in vitro growth and growth factor signaling of murine PTEN-/- cells derived from the prostate (MPPK) or lymph node (MLPK) using serum from lit/lit or lit/+ mice was examined. RESULTS: Body weight and serum GH, IGF-I levels of lit/lit PTEN-/- mice were significantly reduced as compared with lit/+ PTEN-/- mice. At 15 weeks of age, prostate cancer progression of lit/lit PTEN-/- mice was partially delayed as compared with lit/+ PTEN-/- mice. MPPK and MLPK cells growth in vitro with serum from lit/lit mice showed decreased proliferation as compared with serum from lit/+ mice. Suppressed growth in lit/lit serum could be restored by addition of IGF-I, and to a lesser extent, GH. Addition of GH or IGF-I to lit/lit serum increased only activation of AKT while no change in ERK1/2 activation was detected in MPPK cells. Our in vivo and in vitro results suggest that prostate carcinogenesis may be influenced by germ line variation of genes encoding signaling molecules in the GH/IGF-I axis and support the continued development of clinical trials of novel hormonal treatment strategies that target the GH/IGF-I axis for PCa patients. 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 1096. doi:10.1158/1538-7445.AM2011-1096
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.009 | 0.003 |
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".