The Insulin-Like Growth Factor System in Breast Cancer Development (pp. 39-49)
Authors: Walter Zumkeller (Johann Wolfgang Goethe-University, Frankfurt, Germany)
Abstract: Normal and aberrant growth of the mammary gland is under para- and autocrine regulation by hormones and growth factors. Insulin-like growth factors, their receptors and specific binding proteins play a pivotal role in normal mammary gland as well as breast cancer development. Overexpression of IGFs in mammary epithelium leads ultimately to mammary tumour formation whereas genetic ‘knockout’ of IGF-I or the type I IGF receptor results in decreased epithelial growth in the mouse mammary gland. Epidemiologic studies have also implicated IGF-I serum levels with breast cancers in humans. IGF signalling plays an important role in epithelial cell cycle progression in the mammary gland while IGF-binding proteins (IGFBPs) modulate IGF availability both locally and in circulation. IGFBPs also contribute towards remodelling of the extracellular matrix (ECM) and possess pro-apoptotic functions. Thus, IGFs, IGF receptors and IGFBPs are important regulators of epithelial growth in breast cancer. Targeting the IGF system in breast cancer patients may constitute an additional tool in the already available cancer therapy.