Crosstalk between 1,25(OH) 2 -Vitamin D 3 and the growth factors EGF and PDGF-BB: Impact on CYP24A1 expression and cell proliferation.

Autor: Olsson F; Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Center, Box 591, SE-75124, Uppsala, Sweden., Wåhlén E; Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Center, Box 591, SE-75124, Uppsala, Sweden., Heldin J; Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Center, Box 591, SE-75124, Uppsala, Sweden., Söderberg O; Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Center, Box 591, SE-75124, Uppsala, Sweden., Norlin M; Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Center, Box 591, SE-75124, Uppsala, Sweden., Lennartsson J; Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Center, Box 591, SE-75124, Uppsala, Sweden. Electronic address: johan.lennartsson@uu.se.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Dec 03; Vol. 736, pp. 150866. Date of Electronic Publication: 2024 Oct 21.
DOI: 10.1016/j.bbrc.2024.150866
Abstrakt: This study explored the signaling interplay between the vitamin D receptor (VDR) and receptor tyrosine kinases (RTKs). Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF)-BB promotes cell proliferation in normal and cancer cells. At the same time, the active form of vitamin D (1,25(OH) 2 -vitamin D 3 ) inhibits proliferation in some cells. Although EGF receptors (EGFR) and PDGF receptors (PDGFR) activate similar downstream pathways, we found that they interact with VDR signaling in distinct ways. We confirmed that 1,25(OH) 2 -vitamin D 3 induces CYP24A1 gene expression in U2OS, T98G, and U251 cells. We found this to be potentiated when combined with EGF. In contrast, PDGF-BB did not impact 1,25(OH) 2 -vitamin D 3 -induced CYP24A1 expression in U2OS cells. The increase in CYP24A1 expression due to the combined action of EGF and 1,25(OH) 2 -vitamin D 3 was dependent on AKT and ERK1/2 activation. Another VDR-responsive gene, CYP27B1, was unaffected by the addition of EGF, suggesting that EGF may have gene-specific effects on VDR signaling. While PDGF-BB did not influence CYP24A1 expression, 1,25(OH) 2 -vitamin D 3 significantly influenced PDGF-BB-induced receptor phosphorylation and cell proliferation. In summary, we found that EGF, but not PDGF-BB, influenced the expression of the VDR-dependent gene CYP24A1, while 1,25(OH) 2 -vitamin D 3 had an inhibitory effect on PDGFR signaling and proliferation. These findings highlight unique crosstalk between 1,25(OH) 2 -vitamin D 3 signaling and EGF or PDGF-BB.
Competing Interests: Declaration of competing interest The authors have nothing to declare.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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