Vitamin D receptor expression is associated with improved overall survival in human glioblastoma multiforme

Salomón, Débora Gisele; Fermento, María Eugenia; Gandini, Norberto Ariel; Ferronato, María Julia; Arévalo, Julián; Blasco, José; Andrés, Nancy Carolina; Zenklusen, Jean C.; Curino, Alejandro Carlos; Facchinetti, María Marta

doi:10.1007/s11060-014-1416-3

Cited by 34 publications

(40 citation statements)

References 50 publications

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“…Previous studies reported expression of VDR in T98G cells [21,26]. To confirm that significant expression could be detected in our cell cultures, we carried out RT-PCR with human kidney as positive control.…”

Section: Vdr Expression In the T98g Cell Linesupporting

confidence: 63%

Vitamin D Analogues Tacalcitol and Calcipotriol Inhibit Proliferation and Migration of T98G Human Glioblastoma Cells

Emanuelsson

Wikvall

Friman

et al. 2018

Basic Clin Pharma Tox

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The active form of vitamin D (1α,25-dihydroxyvitamin D) acts as a steroid hormone and binds to the vitamin D receptor. This receptor is expressed in most cell types including cells in the central nervous system (CNS). Vitamin D has several functions in the body including effects on brain development, neuroprotection and immunological regulation. It has been shown that vitamin D has antiproliferative activities in different cancer cell lines. Tacalcitol and calcipotriol are synthetic analogues of 1α,25-dihydroxyvitamin D with reduced effect on calcium metabolism. The aim of this study was to analyse the effects of tacalcitol and calcipotriol on cell viability, proliferation and migration in the human glioblastoma cell line T98G. Glioblastoma is the most lethal type of primary tumours in the CNS. Both analogues decreased cell viability and/or growth, dose-dependently, in concentrations between 1 nM and 10 μM. Manual counting indicated suppressive effects by the vitamin D analogues on proliferation. Treatment with tacalcitol strongly suppressed thymidine incorporation, indicating that the vitamin D analogues mainly inhibit proliferation. Also, effects on cell migration were measured with wound-healing assay. Both calcipotriol and tacalcitol reduced the migration rate of T98G cells compared to vehicle-treated cells. However, they had no effect on caspase-3 and -7 activities, suggesting that their mechanism of action does not involve induction of apoptosis. The current results indicate that the vitamin D analogues tacalcitol and calcipotriol strongly reduce proliferation and migration of human glioblastoma T98G cells, suggesting a potential role for this type of compounds in treatment of brain cancer.

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Section: Vdr Expression In the T98g Cell Linesupporting

confidence: 63%

Vitamin D Analogues Tacalcitol and Calcipotriol Inhibit Proliferation and Migration of T98G Human Glioblastoma Cells

Emanuelsson

Wikvall

Friman

et al. 2018

Basic Clin Pharma Tox

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“…In a recent study of human glioma tissue microarrays, the vitamin D receptor was found to be more highly expressed in tumor compared to nonmalignant brain tissues and expression of this receptor was associated with improved outcomes [62]. In this same study, pharmacologic modulation of these receptors in glioma cell lines altered cellular migration.…”

Section: Treatmentmentioning

confidence: 84%

The Role of Glucose Modulation and Dietary Supplementation in Patients With Central Nervous System Tumors

Strowd

Grossman

2015

Curr. Treat. Options in Oncol.

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“…Of note, vitamin D can induce HR expression in keratinocytes, but it is unknown if this transcriptional program is intact in GBM . Nonetheless, vitamin D has been shown to antagonize GBM growth in vitro and in vivo, and VDR protein expression has been demonstrated to be a prognostic factor in GBM . Future studies are warranted to confirm the value of vitamin D–based therapy in GBM and ascertain whether its efficacy can be attributed to upregulation of HR expression.…”

Section: Discussionmentioning

confidence: 99%

Hairless regulates p53 target genes to exert tumor suppressive functions in glioblastoma

Brook

Palade

Maatough

et al. 2018

J of Cellular Biochemistry

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Glioblastoma (GBM) is the most common malignant brain tumor and is associated with a poor prognosis, with most patients living less than a year after diagnosis. Given that GBM nearly always recurs after conventional treatments, there is an urgent need to identify novel molecular targets. Hairless (HR) is a nuclear factor enriched in the skin and has been previously implicated in hair cycling. HR is also highly expressed in the brain, but its significance is unknown. We found that human hairless gene (HR) expression is significantly decreased in all GBM subtypes compared with normal brain tissue and is predictive of prognosis, which suggests that loss of HR expression can contribute to GBM pathogenesis. HR was recently discovered to bind to and regulate p53 responsive elements, and thus we hypothesized that HR may have a tumor suppressive function in GBM by modulating p53 target gene expression. We found that HR indeed regulates p53 target genes, including those implicated in cell cycle progression and apoptosis in the GBM-derived U87 cell line, and restoring HR expression triggered G2/M arrest and apoptosis. An analysis of sequenced genomes from patients with GBM revealed 10 HR somatic mutations in patients with glioma, two of which are located in the histone demethylase domain of HR. These two mutations, P996S and K1004N, were reconstructed and found to have impaired p53 transactivating properties. Collectively, the results of our study suggest that HR has tumor suppressive functions in GBM, which may be clinically relevant and a potential avenue for therapeutic intervention.

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Vitamin D receptor expression is associated with improved overall survival in human glioblastoma multiforme

Cited by 34 publications

References 50 publications

Vitamin D Analogues Tacalcitol and Calcipotriol Inhibit Proliferation and Migration of T98G Human Glioblastoma Cells

Vitamin D Analogues Tacalcitol and Calcipotriol Inhibit Proliferation and Migration of T98G Human Glioblastoma Cells

The Role of Glucose Modulation and Dietary Supplementation in Patients With Central Nervous System Tumors

Hairless regulates p53 target genes to exert tumor suppressive functions in glioblastoma

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