Deregulation of Aurora kinase gene expression in human testicular germ cell tumours

Baldini, Enke; Arlot‐Bonnemains, Yannick; Mottolese, Marcella; Sentinelli, Steno; Antoniani, Barbara; Sorrenti, Salvatore; Salducci, Mauro; Comini, E.; Ulisse, Salvatore; D’Armiento, Massimino

doi:10.1111/j.1439-0272.2009.00987.x

Cited by 18 publications

(17 citation statements)

References 37 publications

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“…AURKC can phosphorylate endogenous histone H3 and evidence suggests that AURKB and AURKC are functionally overlapping 16 . Baldini and colleagues reported deregulated expression of all three aurora kinases in testicular germ cell tumor 17 . The downregulation of AURKC found in our study may result in dysregulated mitosis and more aggressive PTC.…”

Section: Discussionmentioning

confidence: 99%

Molecular pathways associated with mortality in papillary thyroid cancer

Nilubol

Sukchotrat

Zhang

et al. 2011

Surgery

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Background A better understanding of the molecular mechanisms involved in papillary thyroid cancer (PTC)-associated adverse outcome is needed to effectively manage these patients. Our objectives were to identify molecular pathways associated with unfavorable features and outcome in patients with PTC. Method We performed genome-wide expression (GWE) analysis in 64 PTC human tissue samples. Clinical, pathologic and microarray data were analyzed to identify differentially expressed genes/pathways associated with an unfavorable outcome. Gene Set Enrichment Analysis (GSEA) was used to determine which molecular pathways are associated with mortality. Results GWE analysis identified 43, 115 and 40 genes that were significantly differentially expressed by gender, tumor differentiation status and mortality, respectively, with a false discovery rate (FDR) of <5%. For mortality, GSEA revealed 7 enriched pathways including transfer RNA synthesis, mitochondria and oxidative phosphorylation, porphyrin and chlorophyll metabolism, and fatty acid synthesis. Leading edge analysis showed 341 genes significantly involved in the enriched pathways. Cluster analysis using 100 differentially expressed genes showed complete separation of patients by mortality. Conclusions To our knowledge, this is the first GWE analysis of PTC and adverse outcome. Eleven molecular pathways were significantly associated with PTC mortality. A 100-gene signature completely separates patients with and without PTC-associated mortality.

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Section: Discussionmentioning

confidence: 99%

Molecular pathways associated with mortality in papillary thyroid cancer

Nilubol

Sukchotrat

Zhang

et al. 2011

Surgery

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“…These findings have led to their evaluation as a potential target for anticancer therapy (Harrington et al 2004, Hata et al 2005, Matthew et al 2006, Manfredi et al 2007, Arlot-Bonnemains et al 2008, Mountzios et al 2008. TGCTs are characterized, as other types of solid tumors, by aneuploidy, and show an altered expression pattern of the aurora kinases (Oosterhuis et al 1989, Roelofs et al 2000, Chieffi et al 2004, Korkola et al 2008, Baldini et al 2010. This evidence identified the aurora kinases as new potential molecular targets also for the treatment of TGCT, especially against the most aggressive forms resistant to the conventional cisplatin-based chemotherapy (Nichols et al 1994, Horwich et al 2006, Fenner et al 2008.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, Chieffi et al (2004) demonstrated through immunohistochemistry the expression of Aurora-B in 51% of seminoma cells and its association with the Ki-67 proliferation marker. More recently, we demonstrated, by means of quantitative RT-PCR and western blot analysis, that the expression of all three aurora kinases is deregulated in TGCT (Baldini et al 2010). Moreover, the chromosome region where the Aurora-C gene maps (19q13.43) is among the chromosomal regions that are most frequently lost in TGCT (Korkola et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of the aurora kinases suppresses in vitro NT2-D1 cell growth and tumorigenicity

Ulisse¹,

Arlot‐Bonnemains²,

Baldini³

et al. 2009

Journal of Endocrinology

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The aurora kinase family members, Aurora-A, -B, and -C (listed as AURKA, AURKB and AURKC respectively in the HUGO Database), are serine/threonine kinases involved in the regulation of chromosome segregation and cytokinesis, and alterations in their expression are associated with malignant cell transformation and genomic instability. Deregulation of the expression of the aurora kinases has been shown to occur also in testicular germ cell tumors (TGCTs) identifying them as putative anticancer therapeutic targets. We here evaluated the in vitro effects of MK-0457, an aurora kinases inhibitor, on cell proliferation, cell cycle, ploidy, apoptosis, and tumorigenicity on the TGCT-derived cell line NT2-D1. Treatment with MK-0457 inhibited cell proliferation in a time-and dosedependent manner, with IC 50 Z17 . 2G3 . 3 nM. MK-0457 did not affect the expression of the three aurora kinases, but prevented their ability to phosphorylate substrates relevant to the mitotic progression. Time-lapse experiments demonstrated that MK-0457-treated cells entered mitosis but were unable to complete it, presenting after short time the typical features of apoptotic cells. Cytofluorimetric analysis confirmed that the treatment with MK-0457 for 6 h induced NT2-D1 cells accumulation in the G 2 /M phase of the cell cycle and the subsequent appearance of sub-G 0 nuclei. The latter result was further supported by the detection of caspase-3 activation following 24-h treatment with the inhibitor. Finally, MK-0457 prevented the capability of the NT2-D1 cells to form colonies in soft agar. In conclusion, the above findings demonstrate that inhibition of aurora kinase activity is effective in reducing in vitro growth and tumorigenicity of NT2-D1 cells, and indicate its potential therapeutic value for TGCT treatment.

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“…Another important thing in these cells is an altered expression of the aurora kinases family [20], [21], recently observed, associated with malignant cell transformation and genomic instability, [22]. In these studies the aurora Kinase inhibitors were identified and investigated for their capability to reduce “in vitro” NT2 growth and tumorigenicity in order to find a new potential application in cancer therapies [22], [23], [24], [25].…”

Section: Introductionmentioning

confidence: 99%

Non Ionising Radiation as a Non Chemical Strategy in Regenerative Medicine: Ca2+-ICR “In Vitro” Effect on Neuronal Differentiation and Tumorigenicity Modulation in NT2 Cells

et al. 2013

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In regenerative medicine finding a new method for cell differentiation without pharmacological treatment or gene modification and minimal cell manipulation is a challenging goal. In this work we reported a neuronal induced differentiation and consequent reduction of tumorigenicity in NT2 human pluripotent embryonal carcinoma cells exposed to an extremely low frequency electromagnetic field (ELF-EMF), matching the cyclotron frequency corresponding to the charge/mass ratio of calcium ion (Ca2+-ICR). These cells, capable of differentiating into post-mitotic neurons following treatment with Retinoic Acid (RA), were placed in a solenoid and exposed for 5 weeks to Ca2+-ICR. The solenoid was installed in a μ-metal shielded room to avoid the effect of the geomagnetic field and obtained totally controlled and reproducible conditions. Contrast microscopy analysis reveled, in the NT2 exposed cells, an important change in shape and morphology with the outgrowth of neuritic-like structures together with a lower proliferation rate and metabolic activity alike those found in the RA treated cells. A significant up-regulation of early and late neuronal differentiation markers and a significant down-regulation of the transforming growth factor-α (TGF-α) and the fibroblast growth factor-4 (FGF-4) were also observed in the exposed cells. The decreased protein expression of the transforming gene Cripto-1 and the reduced capability of the exposed NT2 cells to form colonies in soft agar supported these last results. In conclusion, our findings demonstrate that the Ca2+-ICR frequency is able to induce differentiation and reduction of tumorigenicity in NT2 exposed cells suggesting a new potential therapeutic use in regenerative medicine.

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Deregulation of Aurora kinase gene expression in human testicular germ cell tumours

Cited by 18 publications

References 37 publications

Molecular pathways associated with mortality in papillary thyroid cancer

Molecular pathways associated with mortality in papillary thyroid cancer

Inhibition of the aurora kinases suppresses in vitro NT2-D1 cell growth and tumorigenicity

Non Ionising Radiation as a Non Chemical Strategy in Regenerative Medicine: Ca2+-ICR “In Vitro” Effect on Neuronal Differentiation and Tumorigenicity Modulation in NT2 Cells

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