title: Insulin and hybrid insulin/IGF receptors are major regulators of breast cancer cells.
abstract: In order to prevent and cure breast cancer it is important to identify and understand the biochemical pathways that are relevant to the biology of this disease. There is evidence, both in vitro and in vivo, that receptor tyrosine kinases play a key role in the formation and progression of breast cancer. The insulin-like growth factors I and II (IGF-I and IGF-II), and their receptor (the IGR-IR) have been well documented in cell culture, animal studies, and humans to play a role in malignant transformation, progression, protection from apoptosis, and metastasis [46]. Also, the hormone insulin (which is very closely related to the IGFs) and its receptor (the IR which is very closely related to the IGR-IR) have been documented both in vitro and in vivo to also play a key role in breast cancer biology [4]. The contribution, however, of the IR to the regulation of breast cancer cell function has not been appreciated. Insulin signals breast cancer cells via its own receptor, and new data indicate that the fetal form of the IR (IR-A) is expressed in breast cancers. IR-A is activated not only by insulin, but also by IGF-II [9,38]. In addition, the IR contributes to formation of hybrid receptors with the IGR-IR (Hybrid-R) [31,32]. This chapter will review these latest developments in our understanding of the IR in breast cancer.
authors.affiliation: Endocrinologia, Dipartimento di Medicina Interna e Medicina Specialistica, University of Catania, Ospedale Garibaldi, 95123 Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Frasca
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pandini
authors.forename: Riccardo
authors.initials: R
authors.lastname: Vigneri
authors.forename: Ira D
authors.initials: ID
authors.lastname: Goldfine