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.
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.
Flint
D J
DJ
Hannah Research Institute, Ayr KA6 5HL, UK.
Boutinaud
M
M
Whitelaw
C B A
CB
Allan
G J
GJ
Kolb
A F
AF
D000818:Animals; D002364:Caseins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics / Q000378:metabolism; D007774:Lactation / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000033:anatomy & histology / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011388:Prolactin / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013002:Somatomedins / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
D002364:Caseins; D018975:Insulin-Like Growth Factor Binding Protein 5; D017451:Receptors, Somatomedin; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D013002:Somatomedins; C494087:Stat3 protein, mouse; D011388:Prolactin; D051057:Proto-Oncogene Proteins c-akt; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D020782:Matrix Metalloproteinases