Effect of 1,25-dihydroxyvitamin D3 on the Wnt pathway in non-malignant colonic cells

The Journal of Steroid Biochemistry and Molecular Biology
Charlotte GröschelEnikő Kállay

Abstract

Epidemiological studies suggest a correlation between vitamin D deficiency and colorectal cancer (CRC) incidence. The majority of sporadic tumors develop from premalignant lesions with aberrant activation of the Wnt/β-catenin signaling pathway. The adenoma cell line LT97 harbors an adenomatous polyposis coli (APC) mutation leading to constitutively active Wnt signaling. In these cells, expression of Wnt target genes leads to increased survival capacity. We hypothesized that 1,25-dihydroyvitamin D3 (1,25-D3), the active form of vitamin D3, promotes differentiation by modulating β-catenin/T-cell factor (TCF) 4-mediated gene transcription. The effect of dietary vitamin D on colonic Wnt signaling was investigated in mice fed either with 100 IU or 2500 IU vitamin D/kg diet. We examined the effect of 1,25-D3 on differentiation by measuring alkaline phosphatase activity. We analyzed mRNA expression of Wnt target genes by real time qRT-PCR. The impact of 1,25-D3 on β-catenin and TCF4 protein expression was assessed by western blot and immunohistochemistry. In LT97 cells, 1,25-D3 increased cellular differentiation and reduced nuclear β-catenin levels. Further, 1,25-D3 decreased mRNA expression of the Wnt target genes BCL-2, Cyclin D1, S...Continue Reading

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Citations

Nov 30, 2016·Scientific Reports·Elisa GaucciSilvia Chichiarelli
Jun 1, 2018·International Journal of Molecular Sciences·Meenakshi UmarAouatef I Chouchane
Jul 25, 2015·Journal of Experimental & Clinical Cancer Research : CR·Bassem RefaatAthar Khojah
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Aug 29, 2020·Cancers·Asunción Fernández-BarralAlberto Muñoz
Sep 13, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Luyan TangJinhua Xu
Nov 25, 2020·Cancers·José Manuel González-SanchoAlberto Muñoz
Mar 27, 2021·The Journal of Steroid Biochemistry and Molecular Biology·Fang YuanYinxiong Li
Mar 25, 2021·Cancer Management and Research·Guangshun SunWeiwei Tang

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