MDA-7/IL-24 functions as a tumor suppressor gene <i>in vivo</i> in transgenic mouse models of breast cancer
Bibliographic record
Abstract
// Mitchell E. Menezes 1 , Xue-Ning Shen 1 , Swadesh K. Das 1,2,3 , Luni Emdad 1,2,3 , Chunqing Guo 1 , Fang Yuan 1 , You-Jun Li 4 , Michael C. Archer 5,6 , Eldad Zacksenhaus 5,7 , Jolene J. Windle 1,2,3 , Mark A. Subler 1 , Yaacov Ben-David 5,8 , Devanand Sarkar 1,2,3 , Xiang-Yang Wang 1,2,3 and Paul B. Fisher 1,2,3 1 Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA 2 VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA 3 VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA 4 Department of Anatomy, Norman Bethune College of Medicine, Jilin University, Changchun, China 5 Departments of Medical Biophysics, University of Toronto, Ontario, Canada 6 Nutritional Sciences, University of Toronto, Ontario, Canada 7 Toronto General Research Institute - University Health Network, Toronto, Ontario, Canada 8 Division of Biology, the Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, China Correspondence to: Paul B. Fisher, email: // Keywords : melanoma differentiation associated gene-7/interleukin-24 (MDA-7/IL-24), MMTV-PyMT mice, MMTV- MDA-7 mice, MMTV- MDA-7 /MMTV- Erbb2 mice, transgenic mice Received : July 06, 2015 Accepted : September 23, 2015 Published : October 12, 2015 Abstract Melanoma differentiation associated gene-7/Interleukin-24 (MDA-7/IL-24) is a novel member of the IL-10 gene family that selectively induces apoptosis and toxic autophagy in a broad spectrum of human cancers, including breast cancer, without harming normal cells or tissues. The ability to investigate the critical events underlying cancer initiation and progression, as well as the capacity to test the efficacy of novel therapeutics, has been significantly advanced by the development of genetically engineered mice (GEMs) that accurately recapitulate specific human cancers. We utilized three transgenic mouse models to better comprehend the in vivo role of MDA-7/IL-24 in breast cancer. Using the MMTV-PyMT spontaneous mammary tumor model, we confirmed that exogenously introducing MDA-7/IL-24 using a Cancer Terminator Virus caused a reduction in tumor burden and also produced an antitumor “bystander” effect. Next we performed xenograft studies in a newly created MMTV- MDA-7 transgenic model that over-expresses MDA-7/IL-24 in the mammary glands during pregnancy and lactation, and found that MDA-7/IL-24 overexpression delayed tumor growth following orthotopic injection of a murine PDX tumor cell line (mPDX) derived from a tumor formed in an MMTV-PyMT mouse. We also crossed the MMTV- MDA-7 line to MMTV- Erbb2 transgenic mice and found that MDA-7/IL-24 overexpression delayed the onset of mammary tumor development in this model of spontaneous mammary tumorigenesis as well. Finally, we assessed the role of MDA-7/IL-24 in immune regulation, which can potentially contribute to tumor suppression in vivo . Our findings provide further direct in vivo evidence for the role of MDA-7/IL-24 in tumor suppression in breast cancer in immune-competent transgenic mice.
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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 | 0.001 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".