Notch- and vitamin D signaling in 1,25(OH)2D3-resistant glioblastoma multiforme (GBM) cell lines

Reichrath, Sandra; Müller, Cornelia; Gleißner, Beate; Pfreundschuh, Michael; Vogt, Thomas; Reichrath, Jörg

doi:10.1016/j.jsbmb.2010.02.028

Cited by 24 publications

(22 citation statements)

References 8 publications

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“…These results are in agreement with those reported by Chen et al (10,32), Reichrath et al (33) and Sivasankaran et al (30). Notably, Chen et al (10,32) and Reichrath et al (33) reported that Notch2 expression varied in different glioma cells, for example astrocytoma and medulloblastoma cells. This indicates that Notch2 may act as an oncogene or tumor suppressor protein, depending on the type of glioma (34–36).…”

Section: Discussionsupporting

confidence: 94%

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Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo

Tian

et al. 2014

Molecular Medicine Reports

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Notch signaling has been reported to be oncogenic or tumor suppressive, depending on the tissue context. To investigate the effects of Notch2 knockdown on U87 human glioma cell proliferation in vitro and in vivo, and the associated mechanisms, U87 cells were stably transfected with p green fluorescent protein (GFP)-V-RS Notch2 short hairpin (sh) RNA plasmid and pGFP-V-RS scramble-shRNA plasmid. The former was referred to as the Notch2-shRNA group and the latter as the negative-shRNA group. mRNA and protein expression, cell proliferation, cell cycle and apoptosis were measured by reverse transcription-polymerase chain reaction, western blot analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis and flow cytometry using propidium iodide, respectively. Tumor volume, tumor weight and cumulative survival rate were determined in a nude mouse xenograft tumor model. Notch2 mRNA and protein expression in the Notch2-shRNA group were reduced by 87.6 and 94.5% compared with the negative-shRNA group (P<0.001). Notch2 knockdown significantly inhibited U87 cell proliferation after three days of culture (P<0.05). Notch2 silencing induced cell cycle arrest at G0/G1 phase by upregulation of p21 protein expression and downregulation of mini chromosome maintenance complex 2 and cyclin-D1 protein expression. Furthermore, knockdown of Notch2 also induced U87 cell apoptosis. On day 50 after inoculation, tumor weight in the Notch2-shRNA group was significantly lower than that in the negative-shRNA group (0.55±0.10 vs. 1.23±0.52 g; P<0.01). The cumulative survival rate was significantly longer in the Notch2-shRNA group compared with the negative-shRNA group (log rank test P=0.01). In conclusion, Notch2 silencing inhibited U87 glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo. Thus, Notch2 may be a key therapeutic target for the treatment of glioma.

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Section: Discussionsupporting

confidence: 94%

“…Studies by Chen et al (10,32), Reichrath et al (33) and Sivasankaran et al (30) have shown that substantial levels of Notch2 mRNA and Notch2 protein are detected in U87 human brain glioma cells. However, it has been reported that Notch2 expression varies in different glioma cells, such as astrocytoma and medulloblastoma cells (10,32–34).…”

Section: Introductionmentioning

confidence: 97%

Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo

Tian

et al. 2014

Molecular Medicine Reports

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“…19 In breast cancers, high notch 1 levels have been associated with poor prognosis, whereas increased notch 2 levels have correlated with greater probability of survival. 20 Increased expression of the notch 3 and notch 4 receptors has been less commonly reported in cancers, but levels of these proteins seem to be elevated in glioblastomas, 21 salivary adenoid cystic carcinomas, 22 breast cancers, 23,24 cervical cancers, 25 and ovarian cancers. 26,27 The mechanistic significance of the expression of each notch receptor in tumours remains to be elucidated.…”

Section: Notch Signalling In Prostatementioning

confidence: 99%

Hypoxia, notch signalling, and prostate cancer

et al. 2013

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The notch signalling pathway is involved in differentiation, proliferation, angiogenesis, vascular remodelling, and apoptosis. Deregulated expression of notch receptors, ligands, and targets is observed in many solid tumours, including prostate cancer. Hypoxia is a common feature of prostate tumours, leading to increased gene instability, reduced treatment response, and increased tumour aggressiveness. The notch signalling pathway is known to regulate vascular cell fate and is responsive to hypoxia-inducible factors. Evidence to date suggests similar, therapeutically exploitable, behaviour of notch-activated and hypoxic prostate cancer cells.

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“…Moreover, the inhibition of Notch signaling by vitamin D analogs also resulted in the reduction of CSCs (unpublished data). However, 1α,25(OH) 2 D 3 did not inhibit the Notch signaling in brain cancer cell lines and did not exhibit anti-proliferative effects in these cells [57]. These data suggest that effects of vitamin D on Notch signaling may differ based on tissue and cellular context.…”

Section: Regulation Of Stem Cell Signaling By Vitamin D In Solid Tumentioning

confidence: 99%

Targeting cancer stem cells in solid tumors by vitamin D

Suh

2015

The Journal of Steroid Biochemistry and Molecular Biology

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Cancer stem cells (CSCs) are a small subset of cells that may be responsible for initiation, progression and recurrence of tumors. Recent studies have demonstrated that CSCs are highly tumorigenic and resistant to conventional chemotherapies, making them a promising target for the development of preventive/therapeutic agents. A single or combination of various markers, such as CD44, EpCAM, CD49f, CD133, CXCR4, ALDH-1 and CD24, were utilized to isolate CSCs fromvarious types of human cancers. Notch, Hedgehog, Wnt, and TGF-β signalingregulate self-renewal and differentiation of normal stem cells andare aberrantly activated in CSCs. In addition, many studies have demonstrated that these stem cell-associated signaling pathways are required for the maintenance of CSCs in differentmalignancies, including breast, colorectal, prostate and pancreatic cancers. Accumulating evidence hasshowninhibitory effects of vitamin D and its analogs on the cancer stem cell signaling pathways, suggesting vitamin D as a potential preventive/therapeutic agent against CSCs.In this review, we summarize recent findings about the roles of Notch, Hedgehog, Wnt, and TGF-β signaling in CSCs as well as the effects of vitamin D on these stem cell signaling pathways.

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Notch- and vitamin D signaling in 1,25(OH)2D3-resistant glioblastoma multiforme (GBM) cell lines

Cited by 24 publications

References 8 publications

Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo

Short hairpin RNA targeting Notch2 inhibits U87 human glioma cell proliferation by inducing cell cycle arrest and apoptosis in vitro and in vivo

Hypoxia, notch signalling, and prostate cancer

Targeting cancer stem cells in solid tumors by vitamin D

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