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Article Dans Une Revue (Data Paper) Stem Cell Reports Année : 2019

s-SHIP Promoter Expression Identifies Mouse Mammary Cancer Stem Cells

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.
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Dates et versions

hal-04276976 , version 1 (09-11-2023)

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Lu Tian, Marie-José Truong, Chann Lagadec, Eric Adriaenssens, Emmanuel Bouchaert, et al.. s-SHIP Promoter Expression Identifies Mouse Mammary Cancer Stem Cells. Stem Cell Reports, 2019, 13 (1), pp.10-20. ⟨10.1016/j.stemcr.2019.05.013⟩. ⟨hal-04276976⟩
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