Vitamin D3 Inhibits Wnt/β-Catenin and mTOR Signaling Pathways in Human Uterine Fibroid Cells

The Journal of Clinical Endocrinology and Metabolism
Ayman Al-HendySunil K Halder

Abstract

Somatic mutations in the Med12 gene are known to activate Wnt/β-catenin signaling in human uterine fibroids (UFs). The objective of the study was to examine the role of vitamin D3 in the modulation of Wnt/β-catenin and mammalian target of rapamycin (mTOR) signaling in human UF cells. Immortalized human UF cells (HuLM) and human primary UF (PUF) cells were treated with increasing concentrations of vitamin D3 and thereafter analyzed using Western blots and immunocytochemistry. Wnt/β-catenin and mTOR signaling proteins in cultured HuLM and PUF cells were measured. UF tumors with Med12 somatic mutations showed an up-regulation of Wnt4 and β-catenin as compared with adjacent myometrium. Vitamin D3 administration reduced the levels of Wnt4 and β-catenin in both HuLM and PUF cells. Vitamin D3 also reduced the expression/activation of mTOR signaling in both cell types. In contrast, vitamin D3 induced the expression of DNA damaged-induced transcription 4 (an inhibitor of mTOR) and tuberous sclerosis genes (TSC1/2) in a concentration-dependent manner in HuLM cells. Furthermore, we observed a concentration-dependent reduction of Wisp1 (Wnt induced signaling protein 1) and flap endonuclease 1 proteins in HuLM cells. Additionally, abrogatio...Continue Reading

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Citations

Jul 28, 2016·Cellular Signalling·Richard T Piszczatowski, Nathan H Lents
Aug 25, 2016·Fertility and Sterility·Tiffany A KatzAyman Al-Hendy
Dec 1, 2017·Human Reproduction Update·Md Soriful IslamPasquapina Ciarmela
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Jan 1, 2020·Clinical Endocrinology·Neda Vishlaghi, Thomas S Lisse
Nov 26, 2019·The Journal of Clinical Endocrinology and Metabolism·Mohamed AliQiwei Yang
May 28, 2020·The Journal of International Medical Research·Saisai LiXueqiong Zhu
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Aug 6, 2020·International Journal of Molecular Sciences·Michał CiebieraAyman Al-Hendy
Feb 13, 2018·Oncology Letters·Charoula MatalliotakiIoannis Matalliotakis
Jul 18, 2018·International Journal of Molecular Sciences·Michał CiebieraGrzegorz Jakiel
Oct 28, 2020·Reproductive Sciences·Michał CiebieraAyman Al-Hendy
Jan 29, 2021·International Journal of Environmental Research and Public Health·Andrea TinelliRadmila Sparić
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Aug 28, 2021·International Journal of Molecular Sciences·Alba Machado-LopezAymara Mas

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