ArticleBreast cancer research : BCR2012
Hyperinsulinemia enhances c-Myc-mediated mammary tumor development and advances metastatic progression to the lung in a mouse model of type 2 diabetes.
Article in Breast cancer research : BCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 95 citations in OpenAlex.
- Insulin receptor expression and its association with hyperinsulinemia in triple negative breast cancer.Journal of the Endocrine Society · 2026Article
- Cardiometabolic disease and cardio-oncology: Insights from iPSC models and tissue engineering.Cell reports. Medicine · 2025Review
- Breast Cancer Cell Line-Specific Responses to Insulin: Effects on Proliferation and Migration.International journal of molecular sciences · 2025Article
- SREBP-1 in obesity-induced breast cancer: mechanisms and therapeutic perspectives.Molecular biology reports · 2025Review
- Breast cancer shares many epidemiological, lifestyle, and local hormonal and metabolic underpinnings with endometrial and ovarian cancer: a narrative review.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2025Review
- Anti-Diabetic Therapies and Cancer: From Bench to Bedside.Biomolecules · 2024Review
- Validation of quercetin in the treatment of colon cancer with diabetes via network pharmacology, molecular dynamics simulations, and in vitro experiments.Molecular diversity · 2024Article
- Genetically proxied glucose-lowering drug target perturbation and risk of cancer: a Mendelian randomisation analysis.Diabetologia · 2023Article
- The Molecular and Genetic Interactions between Obesity and Breast Cancer Risk.Medicina (Kaunas, Lithuania) · 2023Review
- RAGE inhibition blunts insulin-induced oncogenic signals in breast cancer.Breast cancer research : BCR · 2023Article
- Metabolic Profile and Negatively Association Between Insulin Resistance and Metastatic Incidence in Indonesian Primary Invasive Breast Cancer: A Cross-Sectional Study.International journal of general medicine · 2023Article
- The insulin and IGF signaling pathway sustains breast cancer stem cells by IRS2/PI3K-mediated regulation of MYC.Cell reports · 2022Article
- Childhood Obesity: A Potential Key Factor in the Development of Glioblastoma Multiforme.Life (Basel, Switzerland) · 2022Review
- Editorial: Molecular mechanisms in breast cancer progression and metastasis.Frontiers in oncology · 2022Article
- Drug repositioning in drug discovery of T2DM and repositioning potential of antidiabetic agents.Computational and structural biotechnology journal · 2022Review
- Hyperinsulinemia in Obesity, Inflammation, and Cancer.Diabetes & metabolism journal · 2021Review
- Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models.Nature communications · 2021Article
- Benzophenone-3 promotion of mammary tumorigenesis is diet-dependent.Oncotarget · 2020Article
- Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer.Biomolecules · 2020Review
- Hyperinsulinaemia in cancer.Nature reviews. Cancer · 2020Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
introductionHyperinsulinemia, which is common in early type 2 diabetes (T2D) as a result of the chronically insulin-resistant state, has now been identified as a specific factor which can worsen breast cancer prognosis. In breast cancer, a high rate of mortality persists due to the emergence of pulmonary metastases.
methodsUsing a hyperinsulinemic mouse model (MKR+/+) and the metastatic, c-Myc-transformed mammary carcinoma cell line Mvt1, we investigated how high systemic insulin levels would affect the progression of orthotopically inoculated primary mammary tumors to lung metastases.
resultsWe found that orthotopically injected Mvt1 cells gave rise to larger mammary tumors and to a significantly higher mean number of pulmonary macrometastases in hyperinsulinemic mice over a period of six weeks (hyperinsulinemic, 19.4 ± 2.7 vs. control, 4.0 ± 1.3). When Mvt1-mediated mammary tumors were allowed to develop and metastasize for approximately two weeks and were then surgically removed, hyperinsulinemic mice demonstrated a significantly higher number of lung metastases after a four-week period (hyperinsulinemic, 25.1 ± 4.6 vs. control, 7.4 ± 0.42). Similarly, when Mvt1 cells were injected intravenously, hyperinsulinemic mice demonstrated a significantly higher metastatic burden in the lung than controls after a three-week period (hyperinsulinemic, 6.0 ± 1.63 vs. control, 1.5 ± 0.68). Analysis of Mvt1 cells both in vitro and in vivo revealed a significant up-regulation of the transcription factor c-Myc under hyperinsulinemic conditions, suggesting that hyperinsulinemia may promote c-Myc signaling in breast cancer. Furthermore, insulin-lowering therapy using the beta-adrenergic receptor agonist CL-316243 reduced metastatic burden in hyperinsulinemic mice to control levels.
conclusionsHyperinsulinemia in a mouse model promotes breast cancer metastasis to the lung. Therapies to reduce insulin levels in hyperinsulinemic patients suffering from breast cancer could lessen the likelihood of metastatic progression.
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