Histone deacetylase inhibitors upregulate Notch-1 and inhibit growth in pheochromocytoma cells

Adler, Joel T.; Hottinger, Daniel G.; Kunnimalaiyaan, Muthusamy; Chen, Herbert

doi:10.1016/j.surg.2008.08.027

Cited by 47 publications

(50 citation statements)

References 24 publications

(53 reference statements)

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“…It can be speculated that the VPA effect on GSC viability could partially be a consequence of the interference on Notch/Hedgehog cascades, with important implications in glioma therapy. In support to our findings, several reports underlined the mis-regulation of Notch signaling cascade mediated by VPA as a novel strategy for cancer therapy (46,51,52).…”

Section: Discussionsupporting

confidence: 91%

Down-modulation of SEL1L, an Unfolded Protein Response and Endoplasmic Reticulum-associated Degradation Protein, Sensitizes Glioma Stem Cells to the Cytotoxic Effect of Valproic Acid

Cattaneo

Baronchelli

Schiffer³

et al. 2014

Journal of Biological Chemistry

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Background: Valproic acid is considered as a promising anti-cancer therapeutic agent acting on unfolded protein response. SEL1L is an UPR-responsive gene. Results: SEL1L interference synergy enhances VPA cytotoxic effects on glioma stem cells. Conclusion: VPA treatment combined with SEL1L depletion may influence GSC pharmacological response. Significance: Targeting SEL1L in association with valproic acid treatment may improve glioma treatment.

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Section: Discussionsupporting

confidence: 91%

Down-modulation of SEL1L, an Unfolded Protein Response and Endoplasmic Reticulum-associated Degradation Protein, Sensitizes Glioma Stem Cells to the Cytotoxic Effect of Valproic Acid

Cattaneo

Baronchelli

Schiffer³

et al. 2014

Journal of Biological Chemistry

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“…Despite these promising experimental data, however, everolimus does not appear to be an efficient therapeutic modality for ACC in the clinical setting [92]. Notch-signaling might be another example established in our study on recurring PCC [72] that could be exploited in the treatment by e.g., histone deacetylase inhibitors [86].…”

Section: Indirect Targets: Pathways Affected By Micrornasmentioning

confidence: 80%

“…By pathway analysis, overexpressed miR-1225-3p might result in decreased Notch signaling [72]. The relevance of Notch signaling is underlined by in vitro studies on rat PC12 PCC cells where histone deacetylase inhibitors up-regulating Notch-1 inhibited cell proliferation [86]. Notch signaling might thus represent a novel target of PCC treatment.…”

Section: Micrornas In Pheochromocytomasmentioning

confidence: 99%

MicroRNAs in adrenal tumors: relevance for pathogenesis, diagnosis, and therapy

Igaz

Nagy

et al. 2014

Cell. Mol. Life Sci.

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Several lines of evidence support the relevance of microRNAs in both adrenocortical and adrenomedullary (pheochromocytomas) tumors. Significantly differentially expressed microRNAs have been described among benign and malignant adrenocortical tumors and different forms of pheochromocytomas that might affect different pathogenic pathways. MicroRNAs can be exploited as markers of malignancy or disease recurrence. Besides tissue microRNAs, novel data show that microRNAs are released in body fluids, and blood-borne microRNAs can be envisaged as minimally invasive markers of malignancy or prognosis. MicroRNAs might even serve as treatment targets that could expand the rather-limited therapeutic repertoire in the field of adrenal tumors. In this review, we present a critical synopsis of the recent observations made in the field of adrenal tumor-associated microRNAs regarding their pathogenic, diagnostic, and potential therapeutic relevance.

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“…42 The valproic acid-induced activation of Notch1 pathway in PC12 rat pheochromocytoma cell line was associated with differentiation and growth inhibition. 43 'G-protein-coupled receptor signaling' is also involved in several biological processes (eg cell growth, differentiation, synaptic transmission, hormone release and actions, cell migration) in a cellspecific manner. 44 Activation of 'c-Myc-mediated pathway' has also been revealed by Gene Set Enrichment Analysis 40 in malignant pheochromocytomas.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression profiling in benign (sporadic and hereditary) and recurring adrenal pheochromocytomas

et al. 2010

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MicroRNAs are involved in the pathogenesis of several tumors, however, there have been no data on microRNA expression in pheochromocytomas to date. The objective of our study was to perform microRNA expression profiling in sporadic and hereditary benign, and recurring adrenomedullary tumors. Furthermore, the applicability of formalin-fixed paraffin-embedded tissue samples for the analysis of microRNA expression in pheochromocytomas was examined. MicroRNA expression data of three matched frozen and formalin-fixed paraffin-embedded samples were correlated. A total of 21 formalin-fixed paraffin-embedded samples (sporadic benign, multiple endocrine neoplasia 2, von Hippel-Lindau disease, sporadic recurring) were subjected to microRNA expression profiling using microarrays. MicroRNAs with significant differences in expression were validated and sample sizes were extended including tumors from neurofibromatosis type 1 patients by real-time quantitative reverse-transcription PCR (n ¼ 33). MicroRNA target prediction was carried out by TargetScan and MicroCosm Targets. Pathway analysis of targets was performed by Ingenuity Pathway Analysis and DIANA mirPath. Furthermore, microRNA expression profiles of a malignant pheochromocytoma and a pair of primary and recurrent tumors were studied by TaqMan Human MicroRNA Cards. MicroRNA expression correlated well between frozen and formalin-fixed paraffinembedded samples (70-92%). Microarray analysis revealed 16 significantly differentially expressed microRNAs. Five of these were validated by real-time RT-PCR. miR-139-3p, miR-541 and miR-765 were significantly differentially expressed between sporadic benign and von Hippel-Lindau-related pheochromocytomas. Significantly higher expression of miR-885-5p and miR-1225-3p was found in multiple endocrine neoplasia type 2 and sporadic recurring pheochromocytomas, respectively. Pathway analysis revealed the possible involvement of Notch-and G-proteincoupled receptor signaling in tumor recurrence. MicroRNA expression profiles in the primary recurrent and recurring malignant comparisons have been similar. In conclusion, we have proved that formalin-fixed paraffinembedded samples can be used for the analysis of microRNA expression in pheochromocytomas. MicroRNA expression patterns differ between various sporadic, hereditary and recurring tumors and miR-1225-3p may be useful for identifying recurring pheochromocytomas.

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Histone deacetylase inhibitors upregulate Notch-1 and inhibit growth in pheochromocytoma cells

Cited by 47 publications

References 24 publications

Down-modulation of SEL1L, an Unfolded Protein Response and Endoplasmic Reticulum-associated Degradation Protein, Sensitizes Glioma Stem Cells to the Cytotoxic Effect of Valproic Acid

Down-modulation of SEL1L, an Unfolded Protein Response and Endoplasmic Reticulum-associated Degradation Protein, Sensitizes Glioma Stem Cells to the Cytotoxic Effect of Valproic Acid

MicroRNAs in adrenal tumors: relevance for pathogenesis, diagnosis, and therapy

MicroRNA expression profiling in benign (sporadic and hereditary) and recurring adrenal pheochromocytomas

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