TY - JOUR
T1 - DC-SCRIPT deficiency delays mouse mammary gland development and branching morphogenesis
AU - Tang, Chunling
AU - van den Bijgaart, Renske J.E.
AU - Looman, Maaike W.G.
AU - Tel-Karthaus, Nina
AU - de Graaf, Annemarie M.A.
AU - Gilfillan, Susan
AU - Colonna, Marco
AU - Ansems, Marleen
AU - Adema, Gosse J.
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
KW - 3D culture
KW - DC-SCRIPT/Zfp366
KW - Mammary gland morphogenesis
KW - Organoids
UR - http://www.scopus.com/inward/record.url?scp=85068483141&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2019.06.023
DO - 10.1016/j.ydbio.2019.06.023
M3 - Article
C2 - 31265831
AN - SCOPUS:85068483141
SN - 0012-1606
VL - 455
SP - 42
EP - 50
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -