Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Influence of Overexpressed Fibroblast Growth Factor Receptors Towards Vitamin D Receptor Expression and Activity

Version 1 : Received: 20 October 2021 / Approved: 21 October 2021 / Online: 21 October 2021 (10:52:39 CEST)

How to cite: Marchwicka, A.; Jakuszak, A.; Grembowska, A.; Kumari, P.; Marcinkowska, E. The Influence of Overexpressed Fibroblast Growth Factor Receptors Towards Vitamin D Receptor Expression and Activity. Preprints 2021, 2021100304 (doi: 10.20944/preprints202110.0304.v1). Marchwicka, A.; Jakuszak, A.; Grembowska, A.; Kumari, P.; Marcinkowska, E. The Influence of Overexpressed Fibroblast Growth Factor Receptors Towards Vitamin D Receptor Expression and Activity. Preprints 2021, 2021100304 (doi: 10.20944/preprints202110.0304.v1).

Abstract

(1) Background: Many malignancies are driven by mutations which affect the gene for fibroblast growth factor receptor (FGFR) 1. Previously we have documented that signal transduction from FOP2–FGFR1 fusion protein in KG1 cells downregulated the expression of vitamin D receptor (VDR) gene. In this paper we investigated if also other FGFRs were responsible for the regulation of the VDR expression. (2) Methods: We used human myeloid leukemia cells U937, and bone cancer cell line U2OS, and cell transfection methods in order to address the above questions. (3) Results: In myeloid leukemia cells overexpression of FGFR 1-4 caused shift to granulocytic differentiation, upregulated expression of VDR, and sensitized these cells to 1,25-dihydroxyvitamin D (1,25D)-induced monocytic differentiation, while in bone cells, signal transduction activated by FGF1 was not responsible for regulation of VDR expression and activity. (4) Conclusions: Since the overexpression of FGFRs occurs in many neoplasms, it may be reasonable to use 1,25D analogs in these cancers, in which overexpression of FGFRs leads to VDR upregulation.

Keywords

1,25-dihydroxyvitamin D; vitamin D receptor; vitamin D receptor; fibroblast growth factor receptor; signal transduction; differentiation

Subject

MEDICINE & PHARMACOLOGY, Oncology & Oncogenics

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