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Insulin-like growth factors and insulin-like growth factor binding proteins in mammary gland function.

Marshman E, Streuli CH - Breast Cancer Res. (2002)

Bottom Line: Insulin-like growth factor (IGF)-mediated proliferation and survival are essential for normal development in the mammary gland during puberty and pregnancy.IGFs interact with IGF-binding proteins and regulate their function.The present review focuses on the role of IGFs and IGF-binding proteins in the mammary gland and describes how modulation of their actions occurs by association with hormones, other growth factors and the extracellular matrix.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, University of Manchester, UK. emma.marshman@man.ac.uk

ABSTRACT
Insulin-like growth factor (IGF)-mediated proliferation and survival are essential for normal development in the mammary gland during puberty and pregnancy. IGFs interact with IGF-binding proteins and regulate their function. The present review focuses on the role of IGFs and IGF-binding proteins in the mammary gland and describes how modulation of their actions occurs by association with hormones, other growth factors and the extracellular matrix. The review will also highlight the involvement of the IGF axis in breast cancer.

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Related in: MedlinePlus

Insulin-like growth factor-I (IGF-I) signalling networks in the mammary gland. Growth hormone (GH) acting on the growth hormone receptor (GHR) on stromal cells induces IGF-I release, which subsequently acts at the type I insulin-like growth factor receptor (IGF-IR) on epithelial cells to mediate survival and proliferation. Oestrogen can also induce IGF-I expression, which may then act on adjacent mammary epithelial cells. The basement membrane provides an interface between stroma and epithelial cells, and it can contribute to the signals required for mammary development via integrin receptors. Epidermal growth factor (EGF) can synergize with IGF-I, and IGF-I can transactivate the EGF receptor (EGFR). ER, oestrogen receptor.
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Figure 1: Insulin-like growth factor-I (IGF-I) signalling networks in the mammary gland. Growth hormone (GH) acting on the growth hormone receptor (GHR) on stromal cells induces IGF-I release, which subsequently acts at the type I insulin-like growth factor receptor (IGF-IR) on epithelial cells to mediate survival and proliferation. Oestrogen can also induce IGF-I expression, which may then act on adjacent mammary epithelial cells. The basement membrane provides an interface between stroma and epithelial cells, and it can contribute to the signals required for mammary development via integrin receptors. Epidermal growth factor (EGF) can synergize with IGF-I, and IGF-I can transactivate the EGF receptor (EGFR). ER, oestrogen receptor.

Mentions: IGFs are synthesized by stromal cells of the mammary connective tissue (i.e. fibroblasts and adipocytes). This supports the well-known concept that stromal–epithelial interactions are vital for full mammary gland development. IGF-I and IGF-II mRNA are thus expressed in stromal cells, while the IGF-IR is present within the epithelium [10]. The GHR is also present in stroma, and tissue recombination experiments indicate that GHR expression by stromal cells, rather than the epithelium, is essential for mammary development [6]. Moreover, GH induces IGF-I mRNA in isolated epithelium-free mammary stroma [8]. It thus appears that GH activates the GHR within stromal fibroblasts and/or adipocytes, thereby inducing expression of IGF-I, which then acts on the IGF-IR in the epithelium (Fig. 1). Interestingly, a comparison of IGF-I mRNA expression in mammary fat pads with and without glandular epithelium revealed higher stromal expression when the epithelium is present [11]. This suggests the involvement of reciprocal interactions whereby the epithelial cells feedback on the stromal cells to modulate production. One further issue of note is the lack of studies on the effect of IGFs on mammary stromal cells. Since IGF-I is important in regulating adipocyte differentiation in cultured cells [12], this is an area that may deserve future attention.


Insulin-like growth factors and insulin-like growth factor binding proteins in mammary gland function.

Marshman E, Streuli CH - Breast Cancer Res. (2002)

Insulin-like growth factor-I (IGF-I) signalling networks in the mammary gland. Growth hormone (GH) acting on the growth hormone receptor (GHR) on stromal cells induces IGF-I release, which subsequently acts at the type I insulin-like growth factor receptor (IGF-IR) on epithelial cells to mediate survival and proliferation. Oestrogen can also induce IGF-I expression, which may then act on adjacent mammary epithelial cells. The basement membrane provides an interface between stroma and epithelial cells, and it can contribute to the signals required for mammary development via integrin receptors. Epidermal growth factor (EGF) can synergize with IGF-I, and IGF-I can transactivate the EGF receptor (EGFR). ER, oestrogen receptor.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC137936&req=5

Figure 1: Insulin-like growth factor-I (IGF-I) signalling networks in the mammary gland. Growth hormone (GH) acting on the growth hormone receptor (GHR) on stromal cells induces IGF-I release, which subsequently acts at the type I insulin-like growth factor receptor (IGF-IR) on epithelial cells to mediate survival and proliferation. Oestrogen can also induce IGF-I expression, which may then act on adjacent mammary epithelial cells. The basement membrane provides an interface between stroma and epithelial cells, and it can contribute to the signals required for mammary development via integrin receptors. Epidermal growth factor (EGF) can synergize with IGF-I, and IGF-I can transactivate the EGF receptor (EGFR). ER, oestrogen receptor.
Mentions: IGFs are synthesized by stromal cells of the mammary connective tissue (i.e. fibroblasts and adipocytes). This supports the well-known concept that stromal–epithelial interactions are vital for full mammary gland development. IGF-I and IGF-II mRNA are thus expressed in stromal cells, while the IGF-IR is present within the epithelium [10]. The GHR is also present in stroma, and tissue recombination experiments indicate that GHR expression by stromal cells, rather than the epithelium, is essential for mammary development [6]. Moreover, GH induces IGF-I mRNA in isolated epithelium-free mammary stroma [8]. It thus appears that GH activates the GHR within stromal fibroblasts and/or adipocytes, thereby inducing expression of IGF-I, which then acts on the IGF-IR in the epithelium (Fig. 1). Interestingly, a comparison of IGF-I mRNA expression in mammary fat pads with and without glandular epithelium revealed higher stromal expression when the epithelium is present [11]. This suggests the involvement of reciprocal interactions whereby the epithelial cells feedback on the stromal cells to modulate production. One further issue of note is the lack of studies on the effect of IGFs on mammary stromal cells. Since IGF-I is important in regulating adipocyte differentiation in cultured cells [12], this is an area that may deserve future attention.

Bottom Line: Insulin-like growth factor (IGF)-mediated proliferation and survival are essential for normal development in the mammary gland during puberty and pregnancy.IGFs interact with IGF-binding proteins and regulate their function.The present review focuses on the role of IGFs and IGF-binding proteins in the mammary gland and describes how modulation of their actions occurs by association with hormones, other growth factors and the extracellular matrix.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, University of Manchester, UK. emma.marshman@man.ac.uk

ABSTRACT
Insulin-like growth factor (IGF)-mediated proliferation and survival are essential for normal development in the mammary gland during puberty and pregnancy. IGFs interact with IGF-binding proteins and regulate their function. The present review focuses on the role of IGFs and IGF-binding proteins in the mammary gland and describes how modulation of their actions occurs by association with hormones, other growth factors and the extracellular matrix. The review will also highlight the involvement of the IGF axis in breast cancer.

Show MeSH
Related in: MedlinePlus