Mammary gland involution is delayed by activated Akt in transgenic mice

Mol Endocrinol. 2001 Jun;15(6):867-81. doi: 10.1210/mend.15.6.0663.

Abstract

Activation of the antiapoptotic protein kinase Akt is induced by a number of growth factors that regulate mammary gland development. Akt is expressed during mammary gland development, and expression decreases at the onset of involution. To address Akt actions in mammary gland development, transgenic mice were generated expressing constitutively active Akt in the mammary gland under the control of the mouse mammary tumor virus (MMTV) promoter. Analysis of mammary glands from these mice reveals a delay in both involution and the onset of apoptosis. Expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), an inhibitor of matrix metalloproteinases (MMPs), is prolonged and increased in the transgenic mice, suggesting that disruption of the MMP:TIMP ratio may contribute to the delayed mammary gland involution observed in the transgenic mice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Caseins / genetics
  • Caseins / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Immunoblotting
  • Lactation / physiology
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / physiology*
  • Mammary Tumor Virus, Mouse / genetics
  • Mammary Tumor Virus, Mouse / metabolism
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 3 / metabolism
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Milk Proteins / genetics
  • Milk Proteins / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • Caseins
  • DNA-Binding Proteins
  • Milk Proteins
  • Proto-Oncogene Proteins
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor
  • Stat3 protein, mouse
  • Tissue Inhibitor of Metalloproteinase-1
  • Trans-Activators
  • whey acidic proteins
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 3