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Insulin and IGFs in Obesity-Related Breast Cancer

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Obesity and the Metabolic Syndrome are associated with multiple factors that may cause an increased risk for cancer and cancer-related mortality. Factors involved include hyperinsulinemia, hyperglycemia, hyperlipidemia and IGFs. Insulin resistance is also associated with alterations in the levels of proinflammatory cytokines, chemokines, adipokines (leptin, adiponectin) that may also be contributing factors. The insulin family of proteins is ubiquitously expressed and has pleiotropic effects on metabolism and growth. However insulin, IGF-1 and particularly IGF-2 have been identified as tumor promoters in multiple studies. Mouse models have focused on insulin and IGF-1 and their receptors as being involved in tumor progression and metastases. The role of the insulin receptor as either mediating the effects on tumors or as compensating for the insulin-like growth factor receptor has arisen. Its role has been supported by preclinical studies and the importance of insulin resistance and hyperinsulinemia in obesity and early diabetes. Since the focus of this review is the insulin-family we will focus on insulin, IGF-1 and IGF-2.

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Abbreviations

IGF-1:

insulin-like growth factor-1

IGF-2:

insulin-like growth factor-2

IGFBP:

insulin-like growth factor binding protein

MAPK:

mitogen activated protein kinase

ER:

estrogen receptor

PI3K:

phosphotidyinositol 3-kinase

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Authors and Affiliations

  1. Department of Endocrinology, University of Pisa, Via Paradisa 2, 50124, Pisa, Italy

    Valentina Belardi

  2. Division of Endocrinology, Diabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai of Medicine, One Gustave L. Levy Place (lOSS), Atran B4-3S, Box 1055, New York, NY, 10029, USA

    Emily J. Gallagher & Derek LeRoith

  3. Department of Oncology - Translational Medicine, Imclone Systems, a wholly-owned subsidiary of Eli Lilly and company, 450 East 29th Street, New York, NY, 10016, USA

    Ruslan Novosyadlyy

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  1. Valentina Belardi
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  4. Derek LeRoith
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Correspondence to Derek LeRoith.

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Belardi, V., Gallagher, E.J., Novosyadlyy, R. et al. Insulin and IGFs in Obesity-Related Breast Cancer. J Mammary Gland Biol Neoplasia 18, 277–289 (2013). https://doi.org/10.1007/s10911-013-9303-7

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