DC-SCRIPT deficiency delays mouse mammary gland development and branching morphogenesis

Autor: Maaike W. G. Looman, Marco Colonna, Gosse J. Adema, Nina Tel-Karthaus, Annemarie M.A. de Graaf, Marleen Ansems, Susan Gilfillan, Renske J.E. van den Bijgaart, Chunling Tang
Rok vydání: 2019
Předmět:
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
Mammary gland
education
Morphogenesis
Cell Culture Techniques
Estrogen receptor
Biology
behavioral disciplines and activities
Epithelium
03 medical and health sciences
0302 clinical medicine
Breast cancer
Mammary Glands
Animal
Organoid
medicine
Animals
Homeostasis
Molecular Biology
030304 developmental biology
Mice
Knockout
0303 health sciences
Gene Expression Regulation
Developmental
Nuclear Proteins
Epithelial Cells
Cell Biology
Cell Cycle Checkpoints
medicine.disease
DNA-Binding Proteins
Mice
Inbred C57BL
Organoids
medicine.anatomical_structure
Mammary Epithelium
Knockout mouse
Cancer research
Female
Mammary gland morphogenesis
030217 neurology & neurosurgery
Developmental Biology
Transcription Factors
Zdroj: Developmental Biology, 455, 42-50
Developmental Biology, 455, 1, pp. 42-50
ISSN: 0012-1606
Popis: Contains fulltext : 208610.pdf (Publisher’s version ) (Open Access) Mammary glands are unique organs in which major adaptive changes occur in morphogenesis and development after birth. Breast cancer is the most common cancer and a major cause of mortality in females worldwide. We have previously identified the loss of expression of the transcription regulator DC-SCRIPT (Zfp366) as a prominent prognostic event in estrogen receptor positive breast cancer patients. DC-SCRIPT affects multiple transcriptional events in breast cancer cells, including estrogen and progesterone receptor-mediated transcription, and promotes CDKN2B-related cell cycle arrest. As loss of DC-SCRIPT expression appears an early event in breast cancer development, we here investigated the role of DC-SCRIPT in mammary gland development using wild-type and DC-SCRIPT knockout mice. Mice lacking DC-SCRIPT exhibited severe breeding problems and showed significant growth delay relative to littermate wild-type mice. Subsequent analysis revealed that DC-SCRIPT was expressed in mouse mammary epithelium and that DC-SCRIPT deficiency delayed mammary gland morphogenesis in vivo. Finally, analysis of 3D mammary gland organoid cultures confirmed that loss of DC-SCRIPT dramatically delayed mammary organoid branching in vitro. The study shows for the first time that DC-SCRIPT deficiency delays mammary gland morphogenesis in vivo and in vitro. These data define DC-SCRIPT as a novel modulator of mammary gland development.
Databáze: OpenAIRE
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