Insulin-like growth factor binding proteins and mammary gland development

Angara Sureshbabu, Elizabeth Tonner, David J Flint

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Mammary gland development is dependent upon insulin-like growth factors (IGFs) as survival factors. The actions of the IGFs are modulated by a family of IGF-binding proteins (IGFBP1-6). Expression of the IGFBPs is both time-dependent and cell-specific during both the developmental phases and the involution of the mammary gland. Although studied extensively in vitro, understanding the roles of IGFBPs in vivo has been difficult, largely due to the fact that IGFBP knock-out mice have no dramatic phenotypes. This review examines the evidence from in vitro studies and the attempts to examine in vivo actions utilising models with IGFBP deficiency or over-expression. In vitro studies demonstrate that IGFBPs can act by inhibition of the survival effects of IGFs, as well as by enhancing the effects of IGFs. Because the IGFBPs are found associated with the extracellular matrix, a role for IGFBPs as a reservoir of IGFs or, alternatively as a potential barrier to IGFs, thereby restricting their entry into particular tissues or cellular compartments was postulated. We also provide evidence with respect to the IGF-independent actions of the IGFBPs which include receptors, nuclear localization, and interaction with the extracellular matrix and cell surface proteins including integrins. We believe that recent findings place some of the IGFBPs in a larger family of extracellular proteins, the secreted cysteine-rich protein (CCN) family, which have similar structural domains (involved in binding to IGFs, extracellular matrix and integrins) and are heavily implicated in tissue re-modeling and morphogenesis.
LanguageEnglish
Pages781-9
Number of pages9
JournalInternational Journal of Developmental Biology
Volume55
Issue number7-9
DOIs
Publication statusPublished - 2011

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Insulin-Like Growth Factor Binding Proteins
Human Mammary Glands
Somatomedins
Extracellular Matrix
Integrins
CCN Intercellular Signaling Proteins
Insulin-Like Growth Factor Binding Protein 6
Cytoplasmic and Nuclear Receptors
Morphogenesis
Knockout Mice
Cysteine
Membrane Proteins
Phenotype

Keywords

  • apoptosis
  • integrin
  • extracellular matrix
  • proteolysis

Cite this

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abstract = "Mammary gland development is dependent upon insulin-like growth factors (IGFs) as survival factors. The actions of the IGFs are modulated by a family of IGF-binding proteins (IGFBP1-6). Expression of the IGFBPs is both time-dependent and cell-specific during both the developmental phases and the involution of the mammary gland. Although studied extensively in vitro, understanding the roles of IGFBPs in vivo has been difficult, largely due to the fact that IGFBP knock-out mice have no dramatic phenotypes. This review examines the evidence from in vitro studies and the attempts to examine in vivo actions utilising models with IGFBP deficiency or over-expression. In vitro studies demonstrate that IGFBPs can act by inhibition of the survival effects of IGFs, as well as by enhancing the effects of IGFs. Because the IGFBPs are found associated with the extracellular matrix, a role for IGFBPs as a reservoir of IGFs or, alternatively as a potential barrier to IGFs, thereby restricting their entry into particular tissues or cellular compartments was postulated. We also provide evidence with respect to the IGF-independent actions of the IGFBPs which include receptors, nuclear localization, and interaction with the extracellular matrix and cell surface proteins including integrins. We believe that recent findings place some of the IGFBPs in a larger family of extracellular proteins, the secreted cysteine-rich protein (CCN) family, which have similar structural domains (involved in binding to IGFs, extracellular matrix and integrins) and are heavily implicated in tissue re-modeling and morphogenesis.",
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Insulin-like growth factor binding proteins and mammary gland development. / Sureshbabu, Angara; Tonner, Elizabeth; Flint, David J.

In: International Journal of Developmental Biology, Vol. 55, No. 7-9, 2011, p. 781-9.

Research output: Contribution to journalArticle

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