s-SHIP Promoter Expression Identifies Mouse Mammary Cancer Stem Cells.
Animals
Breast Neoplasms
/ etiology
Calcium-Binding Proteins
/ genetics
Cell Self Renewal
/ genetics
Disease Models, Animal
Female
Gene Expression
Gene Expression Profiling
Gene Expression Regulation
Genes, Reporter
Humans
Immunophenotyping
Mammary Glands, Animal
/ metabolism
Mice
Mice, Transgenic
Neoplastic Stem Cells
/ metabolism
Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
/ genetics
Promoter Regions, Genetic
CSC
DLK1
SHIP1
breast cancer
mammary tumor
notch
s-SHIP
transgenic mouse
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
09 07 2019
09 07 2019
Historique:
received:
10
07
2018
revised:
13
05
2019
accepted:
14
05
2019
pubmed:
18
6
2019
medline:
11
6
2020
entrez:
18
6
2019
Statut:
ppublish
Résumé
During normal mammary gland development, s-SHIP promoter expression marks a distinct type of mammary stem cells, at two different stages, puberty and early mid-pregnancy. To determine whether s-SHIP is a marker of mammary cancer stem cells (CSCs), we generated bitransgenic mice by crossing the C3(1)-SV40 T-antigen transgenic mouse model of breast cancer, and a transgenic mouse (11.5kb-GFP) expressing green fluorescent protein from the s-SHIP promoter. Here we show that in mammary tumors originating in these bitransgenic mice, s-SHIP promoter expression enriches a rare cell population with CSC activity as demonstrated by sphere-forming assays in vitro and limiting dilution transplantation in vivo. These s-SHIP-positive CSCs are characterized by lower expression of Delta-like non-canonical Notch ligand 1 (DLK1), a negative regulator of the Notch pathway. Inactivation of Dlk1 in s-SHIP-negative tumor cells increases their tumorigenic potential, suggesting a role for DLK1 in mammary cancer stemness.
Identifiants
pubmed: 31204299
pii: S2213-6711(19)30180-8
doi: 10.1016/j.stemcr.2019.05.013
pmc: PMC6626869
pii:
doi:
Substances chimiques
Calcium-Binding Proteins
0
Dlk1 protein, mouse
0
Inpp5d protein, mouse
EC 3.1.3.86
Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
EC 3.1.3.86
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10-20Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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