INT129115
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Sentences Mentioned In
Key: | Protein | Mutation | Event | Anatomy | Negation | Speculation | Pain term | Disease term |
Overall, our data strongly support the view that one role of loss of p16Ink4 in meningiomagenesis could be to sensitize arachnoid cells to Nf2 loss. | |||||||||||||||
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While CDKN2A downregulation was not sufficient to make cells tumorigenic, the ability to induce tumors in nude mice correlated with p53 inactivation and c-myc overexpression. | |||||||||||||||
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Remarkably, meningiomas developed in double-mutant mice do not show features characteristic of high-grade meningioma suggesting that loss of the p14Arf rather than the p16Ink4a component of the locus is critical for malignant transformation of meningiomas. | |||||||||||||||
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In this study we did not observe tumors related to p16Ink4a loss as the end point was set at 15 months of age. | |||||||||||||||
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This phenotype could to a large extent be attributed to the loss of Arf alone as the Arf null mice showed most of the same traits as the Ink4a-Arf null mice (7) and Ink4a*/* mice showed only a subtle predisposition to spontaneous tumor formation later in life (>15 months) (11). | |||||||||||||||
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Altogether, these data indicate that in the mouse homozygous inactivation of p16ink4 tumor suppressor gene, with retained p19Arf function, synergizes with Nf2 loss in meningioma initiation, but not in meningioma progression.
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Altogether, these data indicate that in the mouse homozygous inactivation of p16ink4 tumor suppressor gene, with retained p19Arf function, synergizes with Nf2 loss in meningioma initiation, but not in meningioma progression.
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Altogether, these data indicate that in the mouse homozygous inactivation of p16ink4 tumor suppressor gene, with retained p19Arf function, synergizes with Nf2 loss in meningioma initiation, but not in meningioma progression.
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Development of frank, metastatic tumors requires combination of expression of k-ras mutant or Ela-SV49TAg with the deficiency of the Ink4a/Arf gene [44,46,47]. | |||||||||||||||
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For instance, mice with both Cre-mediated k-ras mutation and Ink4a/Arf gene deficiency develop metastatic pancreatic ductal adenocarcinomas [44]. | |||||||||||||||
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Here we have shown that Ink4a nullizygosity enhances the incidence of meningioma formation induced by somatic Nf2 loss in arachnoid cells, and that in mice p16ink4a loss is not a critical event associated with malignant progression of meningioma. | |||||||||||||||
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While approximately half of all human tumors contain a mutation or deletion of TP53, the rest of the tumors often have inactivation of p53 through other mechanisms including viral infection, loss of ARF, or overexpression of MDM2 [21]. | |||||||||||||||
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These include chromosomal translocations, gain-of-function mutations activating NOTCH1, deletion of tumour suppressor gene CDKN2A, 6q interstitial losses, and SIL-TAL1 rearrangement [196,198]. | |||||||||||||||
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It has been shown that HDACs inhibitors can selectively induce the expression of less than 10% of genes, some of which are involved in the inhibition of tumor growth (e.g., p21WAF1, p27Kip and p16ink4a) [19, 26, 38]. | |||||||||||||||
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Mesothelioma has an unusual molecular pathology with loss of tumour suppressor genes being the predominant pattern of lesions, especially the P16INK4A, and P14ARF, and NF2 genes, rather than the more common p53 and Rb tumour suppressor genes. | |||||||||||||||
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Replacing defective genes (p53, BRCA1, RB, p16) [35, 38] | |||||||||||||||
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General Comments
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