Hormonal control of IGF-binding protein (IGFBP)-5 and IGFBP-2 secretion during differentiation of the HC11 mouse mammary epithelial cell line

K. Phillips, M.A. Park, L.H. Quarrie, M. Boutinaud, J.D. Lochrie, D.J. Flint, G.J. Allan, J. Beattie

Research output: Contribution to journalArticle

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Abstract

The mouse mammary epithelial cell line HC11 upregulates the synthesis of beta-casein (a differentiation marker) following treatment with the lactogenic hormone mix dexamethasone, insulin and prolactin (DIP). We demonstrate that the basal levels of IGF-binding protein (IGFBP)-5 secreted by undifferentiated HC11 cells are upregulated 10-fold during DIP-induced cellular differentiation whereas the level of the other IGFBP species secreted by HC11 cells (IGFBP-2) is downregulated during this process. As previously reported, the combination of all three of these hormones is required for synthesis of the differentiation marker beta-casein, whereas basal IGFBP-5 secretion is evident in the absence of any hormonal treatment and, unlike beta-casein, secretion of this protein can be stimulated by binary combinations of the hormones (although maximal levels of IGFBP-5 are achieved in the presence of all three lactogenic hormones). Additionally, levels of IGFBP-5 can be increased by DIP treatment under conditions (non-competency of HC11 cultures or presence of epidermal growth factor) where DIP treatment does not increase synthesis of beta-casein. For IGFBP-2, dexamethasone is a potent inhibitor of secretion whilst prolactin stimulated the secretion of this binding protein into the medium. For the IGFBP axis in HC11 cells we conclude that, although the levels of IGFBP-5 and -2 are influenced by the state of cellular differentiation, the hormonal regulation of the levels of these IGFBP species can be dissociated from the regulation of beta-casein synthesis. In a further series of experiments we demonstrate that IGF-I is able to replace insulin in the DIP lactogenic hormone mix and by the use of a specific IGF-I receptor blocking antibody indicate that the action of IGF-I is mediated through the cell surface IGF-I receptor and not by cross-reaction of IGF-I ligand at the insulin receptor. We discuss our data in the context of the potential role of the IGF axis in the process of cell differentiation and illustrate the significance of our findings in the context of the physiology and life cycle of the mammary epithelial cell.
LanguageEnglish
Pages197-208
Number of pages11
JournalJournal of Molecular Endocrinology
Volume31
Issue number1
DOIs
Publication statusPublished - Aug 2003

Fingerprint

Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor Binding Protein 2
Prolactin
Dexamethasone
Caseins
Breast
Epithelial Cells
Insulin
Cell Line
Insulin-Like Growth Factor Binding Proteins
Hormones
Insulin-Like Growth Factor I
IGF Type 1 Receptor
Differentiation Antigens
Blocking Antibodies
Insulin Receptor
Cross Reactions
Life Cycle Stages
Epidermal Growth Factor
Cell Differentiation

Keywords

  • mammary epithelial cell line
  • animal studies
  • proteins
  • cells
  • physiology
  • hormones

Cite this

Phillips, K. ; Park, M.A. ; Quarrie, L.H. ; Boutinaud, M. ; Lochrie, J.D. ; Flint, D.J. ; Allan, G.J. ; Beattie, J. / Hormonal control of IGF-binding protein (IGFBP)-5 and IGFBP-2 secretion during differentiation of the HC11 mouse mammary epithelial cell line. In: Journal of Molecular Endocrinology. 2003 ; Vol. 31, No. 1. pp. 197-208.
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Hormonal control of IGF-binding protein (IGFBP)-5 and IGFBP-2 secretion during differentiation of the HC11 mouse mammary epithelial cell line. / Phillips, K.; Park, M.A.; Quarrie, L.H.; Boutinaud, M.; Lochrie, J.D.; Flint, D.J.; Allan, G.J.; Beattie, J.

In: Journal of Molecular Endocrinology, Vol. 31, No. 1, 08.2003, p. 197-208.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hormonal control of IGF-binding protein (IGFBP)-5 and IGFBP-2 secretion during differentiation of the HC11 mouse mammary epithelial cell line

AU - Phillips, K.

AU - Park, M.A.

AU - Quarrie, L.H.

AU - Boutinaud, M.

AU - Lochrie, J.D.

AU - Flint, D.J.

AU - Allan, G.J.

AU - Beattie, J.

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N2 - The mouse mammary epithelial cell line HC11 upregulates the synthesis of beta-casein (a differentiation marker) following treatment with the lactogenic hormone mix dexamethasone, insulin and prolactin (DIP). We demonstrate that the basal levels of IGF-binding protein (IGFBP)-5 secreted by undifferentiated HC11 cells are upregulated 10-fold during DIP-induced cellular differentiation whereas the level of the other IGFBP species secreted by HC11 cells (IGFBP-2) is downregulated during this process. As previously reported, the combination of all three of these hormones is required for synthesis of the differentiation marker beta-casein, whereas basal IGFBP-5 secretion is evident in the absence of any hormonal treatment and, unlike beta-casein, secretion of this protein can be stimulated by binary combinations of the hormones (although maximal levels of IGFBP-5 are achieved in the presence of all three lactogenic hormones). Additionally, levels of IGFBP-5 can be increased by DIP treatment under conditions (non-competency of HC11 cultures or presence of epidermal growth factor) where DIP treatment does not increase synthesis of beta-casein. For IGFBP-2, dexamethasone is a potent inhibitor of secretion whilst prolactin stimulated the secretion of this binding protein into the medium. For the IGFBP axis in HC11 cells we conclude that, although the levels of IGFBP-5 and -2 are influenced by the state of cellular differentiation, the hormonal regulation of the levels of these IGFBP species can be dissociated from the regulation of beta-casein synthesis. In a further series of experiments we demonstrate that IGF-I is able to replace insulin in the DIP lactogenic hormone mix and by the use of a specific IGF-I receptor blocking antibody indicate that the action of IGF-I is mediated through the cell surface IGF-I receptor and not by cross-reaction of IGF-I ligand at the insulin receptor. We discuss our data in the context of the potential role of the IGF axis in the process of cell differentiation and illustrate the significance of our findings in the context of the physiology and life cycle of the mammary epithelial cell.

AB - The mouse mammary epithelial cell line HC11 upregulates the synthesis of beta-casein (a differentiation marker) following treatment with the lactogenic hormone mix dexamethasone, insulin and prolactin (DIP). We demonstrate that the basal levels of IGF-binding protein (IGFBP)-5 secreted by undifferentiated HC11 cells are upregulated 10-fold during DIP-induced cellular differentiation whereas the level of the other IGFBP species secreted by HC11 cells (IGFBP-2) is downregulated during this process. As previously reported, the combination of all three of these hormones is required for synthesis of the differentiation marker beta-casein, whereas basal IGFBP-5 secretion is evident in the absence of any hormonal treatment and, unlike beta-casein, secretion of this protein can be stimulated by binary combinations of the hormones (although maximal levels of IGFBP-5 are achieved in the presence of all three lactogenic hormones). Additionally, levels of IGFBP-5 can be increased by DIP treatment under conditions (non-competency of HC11 cultures or presence of epidermal growth factor) where DIP treatment does not increase synthesis of beta-casein. For IGFBP-2, dexamethasone is a potent inhibitor of secretion whilst prolactin stimulated the secretion of this binding protein into the medium. For the IGFBP axis in HC11 cells we conclude that, although the levels of IGFBP-5 and -2 are influenced by the state of cellular differentiation, the hormonal regulation of the levels of these IGFBP species can be dissociated from the regulation of beta-casein synthesis. In a further series of experiments we demonstrate that IGF-I is able to replace insulin in the DIP lactogenic hormone mix and by the use of a specific IGF-I receptor blocking antibody indicate that the action of IGF-I is mediated through the cell surface IGF-I receptor and not by cross-reaction of IGF-I ligand at the insulin receptor. We discuss our data in the context of the potential role of the IGF axis in the process of cell differentiation and illustrate the significance of our findings in the context of the physiology and life cycle of the mammary epithelial cell.

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KW - animal studies

KW - proteins

KW - cells

KW - physiology

KW - hormones

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