Limits...
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.

Show MeSH

Related in: MedlinePlus

The interplay between insulin-like growth factor (IGF) and insulin-like growth factor binding proteins (IGFBPs). Interactions between IGF and IGFBPs can reduce free IGF levels, decreasing insulin-like growth factor receptor (IGF-IR) activation and inhibiting cellular response. Associations of IGFBPs with extracellular matrix (ECM) components can reduce the affinity of IGFBP for IGFs, thereby releasing bioactive IGF. The actions of proteases can also increase free IGF levels, since IGFBP fragments have reduced affinity for IGFs. IGFBPs may have direct effects mediated by as yet uncharacterized IGFBP receptors.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC137936&req=5

Figure 2: The interplay between insulin-like growth factor (IGF) and insulin-like growth factor binding proteins (IGFBPs). Interactions between IGF and IGFBPs can reduce free IGF levels, decreasing insulin-like growth factor receptor (IGF-IR) activation and inhibiting cellular response. Associations of IGFBPs with extracellular matrix (ECM) components can reduce the affinity of IGFBP for IGFs, thereby releasing bioactive IGF. The actions of proteases can also increase free IGF levels, since IGFBP fragments have reduced affinity for IGFs. IGFBPs may have direct effects mediated by as yet uncharacterized IGFBP receptors.

Mentions: Since IGFBPs have an equal or greater affinity for IGFs compared with the affinity of the IGF-IR, the presence of IGFBPs could inhibit IGF activity by decreasing levels of free IGFs available to activate the receptor (Fig. 2). Such a mechanism has been proposed based on a study examining the expression of IGFBPs in rat milk during involution. A dramatic increase in the concentration of IGFBP-5 is observed in rat milk 48 hours after the removal of the suckling young [47]. A similar change in the mRNA level occurs at this time, indicating that the IGFBP-5 present in rat milk is derived from the gland and does not enter by translocation from the circulation. Consistent with this, the most abundant IGFBP in the mouse mammary gland is IGFBP-5, expression of which is low during pregnancy and lactation but dramatically increases at involution (unpublished observations). This suggests that IGFBPs act locally within the mammary gland in close proximity to the cells involved in IGFBP production. It has thus been proposed that the presence of IGFBP-5 at involution inhibits the survival function of IGFs, leading to apoptosis.


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

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

The interplay between insulin-like growth factor (IGF) and insulin-like growth factor binding proteins (IGFBPs). Interactions between IGF and IGFBPs can reduce free IGF levels, decreasing insulin-like growth factor receptor (IGF-IR) activation and inhibiting cellular response. Associations of IGFBPs with extracellular matrix (ECM) components can reduce the affinity of IGFBP for IGFs, thereby releasing bioactive IGF. The actions of proteases can also increase free IGF levels, since IGFBP fragments have reduced affinity for IGFs. IGFBPs may have direct effects mediated by as yet uncharacterized IGFBP receptors.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: The interplay between insulin-like growth factor (IGF) and insulin-like growth factor binding proteins (IGFBPs). Interactions between IGF and IGFBPs can reduce free IGF levels, decreasing insulin-like growth factor receptor (IGF-IR) activation and inhibiting cellular response. Associations of IGFBPs with extracellular matrix (ECM) components can reduce the affinity of IGFBP for IGFs, thereby releasing bioactive IGF. The actions of proteases can also increase free IGF levels, since IGFBP fragments have reduced affinity for IGFs. IGFBPs may have direct effects mediated by as yet uncharacterized IGFBP receptors.
Mentions: Since IGFBPs have an equal or greater affinity for IGFs compared with the affinity of the IGF-IR, the presence of IGFBPs could inhibit IGF activity by decreasing levels of free IGFs available to activate the receptor (Fig. 2). Such a mechanism has been proposed based on a study examining the expression of IGFBPs in rat milk during involution. A dramatic increase in the concentration of IGFBP-5 is observed in rat milk 48 hours after the removal of the suckling young [47]. A similar change in the mRNA level occurs at this time, indicating that the IGFBP-5 present in rat milk is derived from the gland and does not enter by translocation from the circulation. Consistent with this, the most abundant IGFBP in the mouse mammary gland is IGFBP-5, expression of which is low during pregnancy and lactation but dramatically increases at involution (unpublished observations). This suggests that IGFBPs act locally within the mammary gland in close proximity to the cells involved in IGFBP production. It has thus been proposed that the presence of IGFBP-5 at involution inhibits the survival function of IGFs, leading to apoptosis.

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