Abstract
Insulin-like growth factor-binding protein 5 (IGFBP-5) mediates involution of the mammary gland. The decrease in DNA content and mammary gland weight which accompanies involution was inhibited by prolactin (PRL) in wild-type but not transgenic mice expressing IGFBP-5. Phospho-STAT5 protein levels were significantly lower in IGFBP-5 transgenic mice during lactation suggesting that IGFBP-5 antagonises PRL signalling in the mammary epithelium. In contrast, phospho-STAT3 levels increased during involution to a similar extent in both wild-type and transgenic mice and were unaffected by PRL. PRL inhibited gene expression of matrix metalloproteinases (MMPs) 3 and 12 but not tissue plasminogen activator or plasmin in wild-type and transgenic animals. The effects of PRL on MMPs appear to be indirect since PRL failed to inhibit MMP-3, -7 or -12 expression in HC-11 cells or in a co-transfection including an activated PRL receptor, STAT5 and a MMP-3-luciferase reporter gene. PRL is a potent inhibitor, both of cell death, an effect which is suppressed by IGFBP-5, and of MMP expression, which is independent of the actions of IGFBP-5.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caseins / genetics
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Caseins / metabolism
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Cell Line
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Cricetinae
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Female
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Fibrinolysin / metabolism
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Gene Expression Regulation, Enzymologic
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Genes, Reporter
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Insulin-Like Growth Factor Binding Protein 5* / genetics
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Insulin-Like Growth Factor Binding Protein 5* / metabolism
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Lactation / physiology*
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Mammary Glands, Animal / anatomy & histology
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Mammary Glands, Animal / physiology*
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Matrix Metalloproteinases / genetics
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Matrix Metalloproteinases / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Transgenic
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Prolactin / metabolism*
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Rats
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Receptors, Somatomedin / genetics
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Receptors, Somatomedin / metabolism
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism
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STAT5 Transcription Factor / metabolism
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Signal Transduction / physiology
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Somatomedins / metabolism
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Tissue Plasminogen Activator / genetics
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Tissue Plasminogen Activator / metabolism
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Transgenes*
Substances
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Caseins
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Insulin-Like Growth Factor Binding Protein 5
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Receptors, Somatomedin
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STAT3 Transcription Factor
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STAT5 Transcription Factor
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Somatomedins
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Stat3 protein, mouse
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Prolactin
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Proto-Oncogene Proteins c-akt
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Tissue Plasminogen Activator
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Fibrinolysin
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Matrix Metalloproteinases