INT129115

Context Info Confidence 0.50 First Reported 2003 Last Reported 2011 Negated 0 Speculated 0 Reported most in Body Documents 16 Total Number 16 Disease Relevance 17.03 Pain Relevance 0.76

nucleoplasm (Cdkn2a) aging (Cdkn2a) DNA binding (Cdkn2a) protein complex (Cdkn2a) cytoplasm (Cdkn2a) nucleolus (Cdkn2a)

Cdkn2a (Mus musculus)

Pain Link Frequency Relevance Heat cytokine 12 95.80 Spinal cord 32 81.92 imagery 251 78.64 Angina 1 75.92 palliative 3 69.20 fifth nerve 16 62.08 trigeminal ganglion 16 55.76 tolerance 7 52.64 fibrosis 27 42.32 cva 11 24.32

Disease Link Frequency Relevance Heat Cancer 778 100.00 Viral Infection 1 99.96 Meningioma 728 99.66 Lung Cancer 7 99.18 Adenocarcinoma 58 98.48 Metastasis 53 98.48 Malignant Neoplastic Disease 43 98.36 Genetic Translocation 1 98.34 Neutrophil Disorders 1 94.64 Carcinoma 27 94.60

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.

Negative_regulation (loss) of p16Ink4

1) Confidence 0.50 Published 2008 Journal Brain Pathology (Zurich, Switzerland) Section Body Doc Link PMC2253711 Disease Relevance 0.91 Pain Relevance 0

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.

Negative_regulation (downregulation) of CDKN2A associated with cancer

2) Confidence 0.48 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3014295 Disease Relevance 0.59 Pain Relevance 0

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.

Negative_regulation (loss) of p14Arf associated with malignant neoplastic disease and meningioma

3) Confidence 0.42 Published 2008 Journal Brain Pathology (Zurich, Switzerland) Section Body Doc Link PMC2253711 Disease Relevance 1.10 Pain Relevance 0

In this study we did not observe tumors related to p16Ink4a loss as the end point was set at 15 months of age.

Negative_regulation (loss) of p16Ink4a associated with cancer

4) Confidence 0.42 Published 2008 Journal Brain Pathology (Zurich, Switzerland) Section Body Doc Link PMC2253711 Disease Relevance 1.12 Pain Relevance 0.03

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).

Negative_regulation (loss) of Arf associated with cancer

5) Confidence 0.42 Published 2008 Journal Brain Pathology (Zurich, Switzerland) Section Body Doc Link PMC2253711 Disease Relevance 1.20 Pain Relevance 0.09

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.

Negative_regulation (retained) of p19Arf associated with meningioma and cancer

6) Confidence 0.42 Published 2008 Journal Brain Pathology (Zurich, Switzerland) Section Body Doc Link PMC2253711 Disease Relevance 1.56 Pain Relevance 0.07

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.

Negative_regulation (inactivation) of p16ink4 associated with meningioma and cancer

7) Confidence 0.42 Published 2008 Journal Brain Pathology (Zurich, Switzerland) Section Body Doc Link PMC2253711 Disease Relevance 1.55 Pain Relevance 0.07

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.

Negative_regulation (synergizes) of p19Arf associated with meningioma and cancer

8) Confidence 0.42 Published 2008 Journal Brain Pathology (Zurich, Switzerland) Section Body Doc Link PMC2253711 Disease Relevance 1.57 Pain Relevance 0.08

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].

Negative_regulation (deficiency) of Ink4a associated with metastasis

9) Confidence 0.37 Published 2006 Journal J Carcinog Section Body Doc Link PMC1559682 Disease Relevance 0.98 Pain Relevance 0

For instance, mice with both Cre-mediated k-ras mutation and Ink4a/Arf gene deficiency develop metastatic pancreatic ductal adenocarcinomas [44].

Negative_regulation (deficiency) of Ink4a associated with adenocarcinoma

10) Confidence 0.37 Published 2006 Journal J Carcinog Section Body Doc Link PMC1559682 Disease Relevance 0.72 Pain Relevance 0

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.

Negative_regulation (loss) of p16ink4a associated with malignant neoplastic disease and meningioma

11) Confidence 0.37 Published 2008 Journal Brain Pathology (Zurich, Switzerland) Section Body Doc Link PMC2253711 Disease Relevance 1.35 Pain Relevance 0.20

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].

Negative_regulation (loss) of ARF associated with cancer and viral infection

12) Confidence 0.23 Published 2011 Journal Journal of Oncology Section Body Doc Link PMC3010739 Disease Relevance 1.29 Pain Relevance 0

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].

Negative_regulation (losses) of CDKN2A associated with cancer and genetic translocation

13) Confidence 0.23 Published 2010 Journal Int Arch Med Section Body Doc Link PMC3016243 Disease Relevance 0.77 Pain Relevance 0

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].

Negative_regulation (inhibition) of p16ink4a associated with cancer

14) Confidence 0.10 Published 2011 Journal Journal of Biomedicine and Biotechnology Section Body Doc Link PMC3004414 Disease Relevance 0.50 Pain Relevance 0

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.

Negative_regulation (loss) of P16INK4A associated with lung cancer and cancer

15) Confidence 0.04 Published 2005 Journal Lancet Section Abstract Doc Link 16054941 Disease Relevance 1.10 Pain Relevance 0.15

Replacing defective genes (p53, BRCA1, RB, p16) [35, 38]

Negative_regulation (Replacing) of p16

16) Confidence 0.02 Published 2003 Journal J Biomed Biotechnol Section Body Doc Link PMC179760 Disease Relevance 0.74 Pain Relevance 0.07

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