Pregnancy-associated plasma protein (PAPP)-A expressed in the mammary gland controls epithelial cell proliferation and differentiation.
Lactation is an important event in all-mammalian species. To investigate the role of pregnancy-associated plasma protein (PAPP)-A in lactogenesis, we determined (i) PAPP-A expression in mouse mammary glands and (ii) the biological functions of PAPP-A in mammary epithelial cells. PAPP-A mRNA level was low during early mid pregnancy and increased during mid-late pregnancy, and then slightly decreased during lactation. Cell proliferation signals, but not differentiation, increased PAPP-A mRNA expression in HC11 mammary epithelial cells. Treatment of recombinant PAPP-A protein stimulated HC11 cell proliferation and suppressed the expression of β-casein mRNA, which is one of the milk proteins and cell differentiation marker. Surprisingly, in forcing expression experiment, PAPP-A increased β-casein mRNA expression. Our data suggest that PAPP-A has different roles on intracellular expressing and extracellular treatment to mammary epithelial cells. Taken together, in early pregnancy, circulating PAPP-A protein might be supplied from other organs and stimulates mammary gland growth. In contrast, during mid-late pregnancy, local PAPP-A expression begins and enhances cell differentiation within mammary epithelial cell.
Department of Medicine and Rheumatology, and Global Center of Excellence Program, International Research Center for Molecular Science in Tooth and Bone Disease, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Makoto
M
Nakasato
Hitoshi
H
Kohsaka
Tetsuya
T
Mizutani
Gen
G
Watanabe
Kazuyoshi
K
Taya
Kentaro
K
Nagaoka
D000818:Animals; D002364:Caseins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007774:Lactation / Q000502:physiology; D008297:Male; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D023421:Models, Animal; D011247:Pregnancy; D011270:Pregnancy, Animal; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D002364:Caseins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011266:Pregnancy-Associated Plasma Protein-A