Prolactin inhibits cell loss and decreases matrix metalloproteinase expression in the involuting mouse mammary gland but fails to prevent cell loss in the mammary glands of mice expressing IGFBP-5 as a mammary transgene

D J Flint, M Boutinaud, C B A Whitelaw, G J Allan, Andreas Kolb

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    22 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)435-448
    Number of pages14
    JournalJournal of Molecular Endocrinology
    Volume36
    Issue number3
    DOIs
    Publication statusPublished - 1 Jun 2006

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    Keywords

    • Animals
    • Caseins
    • Cell Line
    • Cricetinae
    • Female
    • Fibrinolysin
    • Gene Expression Regulation, Enzymologic
    • Genes, Reporter
    • Insulin-Like Growth Factor Binding Protein 5
    • Lactation
    • Mammary Glands, Animal
    • Matrix Metalloproteinases
    • Mice
    • Mice, Inbred C57BL
    • Mice, Inbred CBA
    • Mice, Transgenic
    • Prolactin
    • Proto-Oncogene Proteins c-akt
    • Rats
    • Receptors, Somatomedin
    • STAT3 Transcription Factor
    • STAT5 Transcription Factor
    • Signal Transduction
    • Somatomedins
    • Tissue Plasminogen Activator
    • Transgenes

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