ID4 regulates mammary gland development by suppressing p38MAPK activity

Autor: Chad J. Creighton, Fred Sablitzky, Xiaomei Zhang, Jie Dong, Cathrin Brisken, Amanda McGrath, Myra G. Custorio, Michael T. Lewis, Zhijun Du, Ekaterina Bogoslovskaia, Shaoquan Ji, Shixia Huang, Paul Maliakkal, Yi Li, Marian Caikovski
Předmět:
Mouse
Stem-Cells
Expression
Apoptosis
Ductal Morphogenesis
p38 Mitogen-Activated Protein Kinases
Mice
0302 clinical medicine
Breast cancer
Research Articles
Progesterone
Loop-Helix Proteins
Kinase Inhibitor
Mice
Knockout

Regulation of gene expression
0303 health sciences
Gene knockdown
Estradiol
Wnt signaling pathway
Gene Expression Regulation
Developmental

Immunohistochemistry
Cell biology
Estrogen-Receptor-Alpha
030220 oncology & carcinogenesis
Differentiation
Female
Stem cell
Mammary development
medicine.drug_class
Immunoblotting
Biology
Real-Time Polymerase Chain Reaction
03 medical and health sciences
Wnt
Mammary Glands
Animal

Mice Lacking
Id4
In Situ Nick-End Labeling
medicine
Animals
Breast-Cancer
Molecular Biology
p38MAPK (MAPK14
MAPK11)

Cell Proliferation
030304 developmental biology
Cell growth
Molecular biology
Mice
Inbred C57BL

Bromodeoxyuridine
Estrogen
Inhibitor of Differentiation Proteins
Estrogen receptor alpha
Developmental Biology
Zdroj: Development (Cambridge England)
Popis: The ID family of helix-loop-helix proteins regulates cell proliferation and differentiation in many different developmental pathways, but the functions of ID4 in mammary development are unknown. We report that mouse Id4 is expressed in cap cells, basal cells and in a subset of luminal epithelial cells, and that its targeted deletion impairs ductal expansion and branching morphogenesis as well as cell proliferation induced by estrogen and/or progesterone. We discover that p38MAPK is activated in Id4-null mammary cells. p38MAPK is also activated following siRNA-mediated Id4 knockdown in transformed mammary cells. This p38MAPK activation is required for the reduced proliferation and increased apoptosis in Id4-ablated mammary glands. Therefore, ID4 promotes mammary gland development by suppressing p38MAPK activity.
Databáze: OpenAIRE