ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
Hypothalamic gene transfer of BDNF inhibits breast cancer progression and metastasis in middle age obese mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Brain-cancer interactions outside the CNS.Oncogene · 2026Review
- Review
- The tumor-nerve circuit in breast cancer.Cancer metastasis reviews · 2023Review
- Diets Differently Regulate Tumorigenesis in Young E0771 Syngeneic Breast Cancer Mouse Model.Journal of clinical medicine · 2023Article
- Hypothalamic TrkB.FL overexpression improves metabolic outcomes in the BTBR mouse model of autism.PloS one · 2023Article
- Hypothalamic AAV-BDNF gene therapy improves metabolic function and behavior in theMolecular therapy. Methods & clinical development · 2022Article
- Stimulation of hypothalamic oxytocin neurons suppresses colorectal cancer progression in mice.eLife · 2021Article
- Environmental activation of a hypothalamic BDNF-adipocyte IL-15 axis regulates adipose-natural killer cells.Brain, behavior, and immunity · 2021Article
- Enriched environment enhances NK cell maturation through hypothalamic BDNF in male mice.European journal of immunology · 2021Article
- Serum Cytokine Profiles of Melanoma Patients and Their Association with Tumor Progression and Metastasis.Journal of oncology · 2021Article
- Chronic Isolation Stress Affects Central Neuroendocrine Signaling Leading to a Metabolically Active Microenvironment in a Mouse Model of Breast Cancer.Frontiers in behavioral neuroscience · 2021Article
- Enhancing Effects of Environmental Enrichment on the Functions of Natural Killer Cells in Mice.Frontiers in immunology · 2021Review
- Appetite Regulation of TLR4-Induced Inflammatory Signaling.Frontiers in endocrinology · 2021Review
- EO771, is it a well-characterized cell line for mouse mammary cancer model? Limit and uncertainty.Cancer medicine · 2020Review
- Adipose PTEN acts as a downstream mediator of a brain-fat axis in environmental enrichment.Comprehensive psychoneuroendocrinology · 2020Article
- Regulation of aging and cancer by enhanced environmental activation of a hypothalamic-sympathoneural-adipocyte axis.Translational cancer research · 2020Article
- Article
- MicroRNA-496 suppresses tumor cell proliferation by targeting BDNF in osteosarcoma.Experimental and therapeutic medicine · 2020Article
- Improvements to Healthspan Through Environmental Enrichment and Lifestyle Interventions: Where Are We Now?Frontiers in neuroscience · 2020Review
- Enriched environment inhibits breast cancer progression in obese models with intact leptin signaling.Endocrine-related cancer · 2019Article
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Authors and funding
6 authors.
Funding
Abstract
Activation of the hypothalamus-adipocyte axis is associated with an antiobesity and anticancer phenotype in animal models of melanoma and colon cancer. Brain-derived neurotrophic factor (BDNF) is a key mediator in the hypothalamus leading to preferential sympathoneural activation of adipose tissue and the ensuing resistance to obesity and cancer. Here, we generated middle age obese mice by high fat diet feeding for a year and investigated the effects of hypothalamic gene transfer of BDNF on a hormone receptor-positive mammary tumor model. The recombinant adeno-associated viral vector-mediated overexpression of BDNF led to marked weight loss and decrease of adiposity without change of food intake. BDNF gene therapy improved glucose tolerance, alleviated steatosis, reduced leptin level, inhibited mouse breast cancer EO771 growth, and prevented the metastasis. The reduced tumor growth in BDNF-treated mice was associated with reduced angiogenesis, decreased proliferation, increased apoptosis, and reduced adipocyte recruitment and lipid accumulation. Moreover, BDNF gene therapy reduced inflammation markers in the hypothalamus, the mammary gland, the subcutaneous fat, and the mammary tumor. Our results suggest that manipulating a single gene in the brain may influence multiple mechanisms implicated in obesity-cancer association and provide a target for the prevention and treatment of both obesity and cancer.
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