ArticleBreast cancer research : BCR2015
Mammary gland tumor promotion by chronic administration of IGF1 and the insulin analogue AspB10 in the p53R270H/⁺WAPCre mouse model.
Article in Breast cancer research : BCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Treatment with insulin (analogues) and breast cancer risk in diabetics; a systematic review and meta-analysis of in vitro, animal and human evidence.Breast cancer research : BCR · 2015Pooled it
- Review
- Identification of the molecular mechanism of insulin-like growth factor-1 (IGF-1): a promising therapeutic target for neurodegenerative diseases associated with metabolic syndrome.Cell & bioscience · 2023Review
- Effects of Pubertal Exposure to Butyl Benzyl Phthalate, Perfluorooctanoic Acid, and Zeranol on Mammary Gland Development and Tumorigenesis in Rats.International journal of molecular sciences · 2022Article
- Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer.Nature communications · 2021Article
- Diabetes, Body Fatness, and Insulin Prescription Among Adolescents and Young Adults with Cancer.Journal of adolescent and young adult oncology · 2021Article
- Mammary Tumors Growing in the Absence of Growth Hormone Are More Sensitive to Doxorubicin Than Wild-Type Tumors.Endocrinology · 2021Article
- Increased insulin receptor binding and increased IGF-1 receptor binding are linked with increased growth of L6hIR cell xenografts in vivo.Scientific reports · 2020Article
- Effects of insulin and analogues on carcinogen-induced mammary tumours in high-fat-fed rats.Endocrine connections · 2018Article
- The association of diabetes mellitus and insulin treatment with expression of insulin-related proteins in breast tumors.BMC cancer · 2018Article
- Safety study: is there a pathologic IGF-1, PDGF and TGF-β cytokine expression caused by adjunct BMP-7 in tibial and femoral non-union therapy?Therapeutics and clinical risk management · 2018Article
- Insulin-like growth factor 1 receptor activation promotes mammary gland tumor development by increasing glycolysis and promoting biomass production.Breast cancer research : BCR · 2017Article
- Insulin, insulin receptors, and cancer.Journal of endocrinological investigation · 2016Review
- Non-metabolisable insulin glargine does not promote breast cancer growth in a mouse model of type 2 diabetes.Diabetologia · 2016Article
- Cellular adhesome screen identifies critical modulators of focal adhesion dynamics, cellular traction forces and cell migration behaviour.Scientific reports · 2016Article
- Alternative signaling network activation through different insulin receptor family members caused by pro-mitogenic antidiabetic insulin analogues in human mammary epithelial cells.Breast cancer research : BCR · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionInsulin analogues are structurally modified molecules with altered pharmaco-kinetic and -dynamic properties compared to regular human insulin used by diabetic patients. While these compounds are tested for undesired mitogenic effects, an epidemiological discussion is ongoing regarding an association between insulin analogue therapy and increased cancer incidence, including breast cancer. Standard in vivo rodent carcinogenesis assays do not pick up this possible increased carcinogenic potential.
methodsHere we studied the role of insulin analogues in breast cancer development. For this we used the human relevant mammary gland specific p53R270H/⁺WAPCre mouse model. Animals received life long repeated treatment with four different insulin (-like) molecules: normal insulin, insulin glargine, insulin X10 (AspB10) or insulin-like growth factor 1 (IGF1).
resultsInsulin-like molecules with strong mitogenic signaling, insulin X10 and IGF1, significantly decreased the time for tumor development. Yet, insulin glargine and normal insulin, did not significantly decrease the latency time for (mammary gland) tumor development. The majority of tumors had an epithelial to mesenchymal transition phenotype (EMT), irrespective of treatment condition. Enhanced extracellular signaling related kinase (Erk) or serine/threonine kinase (Akt) mitogenic signaling was in particular present in tumors from the insulin X10 and IGF1 treatment groups.
conclusionsThese data indicate that insulin-like molecules with enhanced mitogenic signaling increase the risk of breast cancer development. Moreover, the use of a tissue specific cancer model, like the p53R270H/⁺WAPCre mouse model, is relevant to assess the intrinsic pro-carcinogenic potential of mitogenic and non-mitogenic biologicals such as insulin analogues.
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