First Author | Tang C | Year | 2020 |
Journal | Dev Biol | Volume | 463 |
Issue | 2 | Pages | 101-109 |
PubMed ID | 32422143 | Mgi Jnum | J:292316 |
Mgi Id | MGI:6448028 | Doi | 10.1016/j.ydbio.2020.05.001 |
Citation | Tang C, et al. (2020) DC-SCRIPT affects mammary organoids branching morphogenesis by modulating the FGFR1-pERK signaling axis. Dev Biol 463(2):101-109 |
abstractText | Loss of expression of the transcription regulator DC-SCRIPT (Zfp366) is a prominent prognostic event in estrogen receptor-positive breast cancer patients. Studying the inherent link between breast morphogenesis and tumorigenesis, we recently reported that DC-SCRIPT affects normal mammary branching morphogenesis and mammary epithelium homeostasis. Here we investigated the molecular mechanism involved in DC-SCRIPT mediated regulation of FGF2 induced mammary branching morphogenesis in a 3D organoid culture system. Our data show that the delayed mammary organoid branching observed in DC-SCRIPT(-/-) organoids cannot be compensated for by increasing FGF2 levels. Interestingly, FGFR1, the dominant FGF2 receptor, was expressed at a significantly lower level in basal epithelial cells of DC-SCRIPT deficient organoids relative to wildtype organoids. A potential link between DC-SCRIPT and FGFR1 was further supported by the predicted locations of the DC-SCRIPT DNA binding motif at the Fgfr1 gene. Moreover, ERK1/2 phosphorylation downstream of the FGFR1 pathway was decreased in basal epithelial cells of DC-SCRIPT deficient organoids. Altogether, this study shows a relationship between DC-SCRIPT and FGFR1 related pERK signaling in modulating the branching morphogenesis of mammary organoids in vitro. |