The role of IGFBP-5 in mammary gland development and involution |
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Authors: | Allan Gordon J Beattie James Flint David J |
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Institution: | Hannah Research Institute, Ayr. KA65HL, Scotland, UK. allang@hri.sari.ac.uk |
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Abstract: | 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. |
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