ArticleEndocrine-related cancer2013
Hyperinsulinemia promotes metastasis to the lung in a mouse model of Her2-mediated breast cancer.
Article in Endocrine-related cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer.The Cochrane database of systematic reviews · 2025Pooled it
- Diabetes mellitus and prognosis in women with breast cancer: A systematic review and meta-analysis.Medicine · 2016Pooled it
- Impact of Diabetes, Insulin, and Metformin Use on the Outcome of Patients With Human Epidermal Growth Factor Receptor 2-Positive Primary Breast Cancer: Analysis From the ALTTO Phase III Randomized Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017 · on this mapTrial
- Sex and Gender Perspective in Obesity and Gastric Cancer.The world journal of men's health · 2026Review
- Breast Cancer Cell Line-Specific Responses to Insulin: Effects on Proliferation and Migration.International journal of molecular sciences · 2025Article
- Article
- RAGE inhibition blunts insulin-induced oncogenic signals in breast cancer.Breast cancer research : BCR · 2023Article
- The insulin and IGF signaling pathway sustains breast cancer stem cells by IRS2/PI3K-mediated regulation of MYC.Cell reports · 2022Article
- Fertility-Sparing Treatment for Atypical Endometrial Hyperplasia and Endometrial Cancer: A Cochrane Systematic Review Protocol.Advances in therapy · 2021Article
- Hyperinsulinemia in Obesity, Inflammation, and Cancer.Diabetes & metabolism journal · 2021Review
- Benzophenone-3 promotion of mammary tumorigenesis is diet-dependent.Oncotarget · 2020Article
- Hyperinsulinaemia in cancer.Nature reviews. Cancer · 2020Review
- Hepatic lipids promote liver metastasis.JCI insight · 2020Article
- Article
- Diabetes and cancer: Epidemiological and biological links.World journal of diabetes · 2020Review
- Obesity, Type 2 Diabetes, and Cancer Risk.Frontiers in oncology · 2020Review
- Treatment of ErbB2 breast cancer by mitochondrial targeting.Cancer & metabolism · 2020Article
- Insulin Enhances Migration and Invasion in Prostate Cancer Cells by Up-Regulation of FOXC2.Frontiers in endocrinology · 2019Article
- Silencing vimentin expression decreases pulmonary metastases in a pre-diabetic mouse model of mammary tumor progression.Oncogene · 2017Article
- Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions.Cancer discovery · 2016Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The Her2 oncogene is expressed in ∼25% of human breast cancers and is associated with metastatic progression and poor outcome. Epidemiological studies report that breast cancer incidence and mortality rates are higher in women with type 2 diabetes. Here, we use a mouse model of Her2-mediated breast cancer on a background of hyperinsulinemia to determine how elevated circulating insulin levels affect Her2-mediated primary tumor growth and lung metastasis. Hyperinsulinemic (MKR(+/+)) mice were crossed with doxycycline-inducible Neu-NT (MTB/TAN) mice to produce the MTB/TAN/MKR(+/+) mouse model. Both MTB/TAN and MTB/TAN/MKR(+/+) mice were administered doxycycline in drinking water to induce Neu-NT mammary tumor formation. In tumor tissues removed at 2, 4, and 6 weeks of Neu-NT overexpression, we observed increased tumor mass and higher phosphorylation of the insulin receptor/IGF1 receptor, suggesting that activation of these receptors in conditions of hyperinsulinemia could contribute to the increased growth of mammary tumors. After 12 weeks on doxycycline, although no further increase in tumor weight was observed in MTB/TAN/MKR(+/+) compared with MTB/TAN mice, the number of lung metastases was significantly higher in MTB/TAN/MKR(+/+) mice compared with controls (MTB/TAN/MKR(+/+) 16.41±4.18 vs MTB/TAN 5.36±2.72). In tumors at the 6-week time point, we observed an increase in vimentin, a cytoskeletal protein and marker of mesenchymal cells, associated with epithelial-to-mesenchymal transition and cancer-associated fibroblasts. We conclude that hyperinsulinemia in MTB/TAN/MKR(+/+) mice resulted in larger primary tumors, with more mesenchymal cells and therefore more aggressive tumors with more numerous pulmonary metastases.
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