Journal of Mammary Gland Biology and Neoplasia

, Volume 13, Issue 4, pp 381–406 | Cite as

IGF and Insulin Receptor Signaling in Breast Cancer

  • Antonino BelfioreEmail author
  • Francesco Frasca


Major molecular abnormalities in breast cancer include the deregulation of several components of the IGF system. It is well recognized that the epithelial breast cancer cells commonly overexpress the IGF-I receptor while IGF-II is expressed by the tumor stroma. In view to the fact that the IGF-IR has mitogenic, pro-invasive and anti-apoptotic effects and mediates resistance to a variety of anti-cancer therapies, breast cancer is expected to be a candidate to therapeutic approaches aimed to inhibit the IGF-IR. However, there is increasing awareness that IGF system in cancer undergoes signal diversification by various mechanisms. One of these mechanisms is the aberrant expression of insulin receptor (IR) isoform A (IR-A), which is a high affinity receptor for both insulin and IGF-II, in breast cancer cells. Moreover, overexpression of both IGF-IR and IR-A in breast cancer cells, leads to overexpression of hybrid IR/IGF-IR receptors (HRs) as well. Upon binding to IGF-II, both IR-A and HRs may activate unique signaling patterns, which predominantly mediate proliferative effects. A better understanding of IGF system signal diversification in breast cancer has important implications for cancer prevention measures, which should include control of insulin resistance and associated hyperinsulinemia. Moreover, in addition to the IGF-IR, both IR-A and HRs should be also considered as molecular targets for anti-cancer therapies.


Breast cancer Insulin receptor IGF-I receptor IGF-I IGF-II IGF system 



Thymoma viral proto-oncogene 1


Associate protein substrate


Ataxia telangiectasia mutated


Bcl-2-associated death promoter


B-cell lymphoma 2


Basal cell lymphoma-extra large


Breast and ovarian cancer gene 1, early onset


Cas-Br-M (murine) ecotropic retroviral transforming sequence


Cyclin-dependent kinase 4




4E-binding protein 1


Epidermal growth factor receptor


Human epidermal growth factor receptor-2


Estrogen receptor


Mitogen activated protein kinases


Embryonic stem cells


Focal adhesion kinase


Forkhead in human rabdomyosarcoma


GRB2-associated binding protein 1


Guanosine diphosphate


Growth hormone


Glucose transporter protein 4




Hypoxia inducible factor 1


IR/IGF-IR hybrid A


IR/IGF-IR hybrid B


IR/IGF-IR hybrid receptors


Insulin-like growth factor binding protein 3


IGF-I receptor


Insulin-like growth factor I


Insulin-like growth factor II


Insulin-like growth factors


Insulin receptor


Insulin receptor isoform A


Insulin receptor isoform B


Insulin receptor-related receptor


Jun N terminal kinase


Loss of genomic imprinting


Mitotic arrest deficient 2


Matrix metalloprotease


Mouse mammary tumor virus


Mitogen activated protein kinase




Mannose-6-phosphate/IGF-II receptor


Son of sevenless protein homolog


Mammalian target of rapamycin


Overall survival


Protein kinase B


Protein kinase C


Pleckstrin homology


Phosphatidylinositol 3-kinase


Protein kinase C


3-Phosphoinositide-dependent protein kinase 1


Phosphatidylinositol (3,4,5)-trisphosphate


Harvey rat sarcoma virus oncogene 1


Relapse free survival


Ribosomal S6 kinase 1


Rous sarcoma oncogene


Src-homology 2 domain


Src/collagen homology proteins


Tyrosine kinase C receptor



We thank Prof. Riccardo Vigneri (University of Catania, Italy) for his constant support and advice.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Endocrinology, Department of Clinical and Experimental MedicineUniversity of CatanzaroCatanzaroItaly
  2. 2.Endocrinology, Department of Internal Medicine and Medical SpecialtiesUniversity of CataniaCataniaItaly

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