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 language | English |
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Pages (from-to) | 435-448 |
Number of pages | 14 |
Journal | Journal of Molecular Endocrinology |
Volume | 36 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Jun 2006 |
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