The role of IGFBP-5 in mammary gland development and involution

• Published in: Domestic animal endocrinology 2004-10, Vol.27 (3), p.257-266
• Main Authors: Allan, Gordon J., Beattie, James, Flint, David J.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - physiology; binding proteins; Cell Differentiation - physiology; cell proliferation; Extracellular matrix; Extracellular Matrix - physiology; Female; IGFBP-5; Insulin-like growth factor binding protein; insulin-like growth factor binding protein 5; Insulin-Like Growth Factor Binding Protein 5 - physiology; Insulin-Like Growth Factor Binding Proteins - physiology; insulin-like growth factor I; Insulin-Like Growth Factor I - physiology; Lactation - physiology; literature reviews; mammary development; Mammary gland; mammary glands; Mammary Glands, Animal - cytology; Mammary Glands, Animal - growth & development; Mammary Glands, Animal - physiology; mammary involution; Mice; Mice, Transgenic; physiological regulation; tissue remodelling; transgenic animals; Transgenic mice
• ISSN: 0739-7240; 1879-0054
• DOI: 10.1016/j.domaniend.2004.06.009

Insulin-like growth factor-I (IGF-I) plays an important role as a survival factor during mammary gland development and remodelling during involution of the mature/lactating mammary gland, and elevated concentrations have been associated with increased risk of breast cancer. The actions of IGF-I are modulated by a family of binding proteins (IGFBPs) and we have shown that IGFBP-5 is associated with cell death in the mammary gland and more recently provided the first evidence that it is causally related to apoptosis of the mammary gland. A transgenic mouse expressing IGFBP-5 on a mammary-specific promoter led to impaired mammary development involving inhibition of IGF-signalling and involving members of the Bcl-2 family. Subsequent studies in vitro and in vivo using exogenous IGFBP-5 treatment have added support to this concept. Although the effects of IGFBP-5 did appear to involve inhibition of IGF action, a role for IGF-independent effects cannot be ruled out. Such IGF-independent effects involve potential interactions with components of the extracellular matrix involved in tissue remodelling including plasminogen activator inhibitor-1 (PAI-1). In addition, intracellular events involving nuclear localisation of IGFBP-5 have been shown to have the ability to inhibit cell proliferation. Thus, IGFBP-5 seems important for regulating both apoptosis and cell proliferation in the mammary gland during development and post-lactation involution.