Mammary gland differentiation inversely correlates with GDF-8 expression.
GDF-8 is recognised as an inhibitor of muscle cell growth and differentiation. Although initially thought to be restricted to muscle cells it is now accepted that GDF-8 expression has a broader tissue distribution. We demonstrate GDF-8 expression in the mouse mammary gland, which is predominantly associated with epithelial cells and displays an inverse correlation to the differentiated state of the gland. Specifically, the highest GDF-8 mRNA levels correlate with periods of maximal ductal growth, diminish as pregnancy progressed and are down-regulated to minimal levels by the onset of lactation as the epithelium differentiates. A similar profile is observed for both GDF-8 protein processing and reflects Smad2/3 phosphorylation profile. However, in contrast to muscle cells, GDF-8 neither reduces proliferation nor induces p21 expression levels in mammary epithelial cells. These data implicate a role for GDF-8 in mammary epithelial cell differentiation and demonstrate that GDF-8 has cell-type specific activities.
Manickam
Ravikumar
R
Division of Gene Function and Development, Roslin Institute, Roslin, Edinburgh, United Kingdom.
Pena
Ramona N
RN
Whitelaw
C Bruce A
CB
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D007774:Lactation / Q000523:psychology*; D008321:Mammary Glands, Animal / Q000254:growth & development*; D051379:Mice; D032342:Muscle Cells / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis*; D055435:Myostatin / Q000096:biosynthesis*; D009928:Organ Specificity / Q000502:physiology; D011247:Pregnancy / Q000502:physiology*; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism
C525912:Mstn protein, mouse; D009124:Muscle Proteins; D055435:Myostatin; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse