INT144701

Context Info Confidence 0.75 First Reported 2006 Last Reported 2011 Negated 2 Speculated 0 Reported most in Body Documents 15 Total Number 15 Disease Relevance 8.42 Pain Relevance 0.53

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

Anatomy Link Frequency lungs 1 Cdkn2a (Mus musculus)

Pain Link Frequency Relevance Heat melanocortin 1 receptor 61 99.92 Arthritis 108 98.40 tolerance 10 88.16 rheumatoid arthritis 54 87.84 cytokine 34 53.24 Inflammation 59 52.84 Inflammatory response 2 43.44 fibrosis 20 20.64 metalloproteinase 11 18.80 agonist 8 5.00

Disease Link Frequency Relevance Heat Cancer 423 100.00 Aging 129 99.92 Melanoma 28 98.48 Arthritis 112 98.40 Targeted Disruption 92 98.16 Sarcoma 19 97.76 Apoptosis 122 96.76 Skin Cancer 154 95.16 Impaired Glucose Tolerance 14 88.80 Rheumatoid Arthritis 54 87.84

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Melan-a cells are functionally Ink4a-Arf null, expressing neither p16INK4A nor ARF proteins (Sviderskaya et al., 2002).

Neg (neither) Gene_expression (expressing) of p16INK4A

1) Confidence 0.75 Published 2009 Journal Pigment Cell & Melanoma Research Section Body Doc Link PMC2784899 Disease Relevance 0.15 Pain Relevance 0

Studying cells at different phases of transformation, we could show that an early event during transformation was the loss of expression of the CDKN2A locus, followed by inactivation of p53 and overexpression of c-myc.

Gene_expression (expression) of CDKN2A

2) Confidence 0.63 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3014295 Disease Relevance 0.58 Pain Relevance 0

Notably, hypermethylation of the CDKN2A promoter region has been shown to lead to loss of p16 expression in 19% of primary and 33% metastatic melanomas.[59] DNA methyltransferase(DNMT) inhibitors namely 5-azacytidine, 5-aza-20-deoxycytidine(decitabine), fazarabine, and dihydro-5-azacytidine have been extensively studied.

Gene_expression (expression) of p16 associated with melanoma

3) Confidence 0.58 Published 2010 Journal Journal of Carcinogenesis Section Body Doc Link PMC2862505 Disease Relevance 0.84 Pain Relevance 0

Sequencing of p16ink4a, k-ras and Rb cDNA

Gene_expression (cDNA) of p16ink4a

4) Confidence 0.58 Published 2006 Journal J Carcinog Section Body Doc Link PMC1559682 Disease Relevance 0.67 Pain Relevance 0

Two pathways are known to induce cell cycle arrest and senescence: the P16-Rb and P53-P21 pathways.

Gene_expression (pathways) of P16 associated with aging

5) Confidence 0.56 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2884035 Disease Relevance 0.87 Pain Relevance 0

Lack of p16 did not rescue the angiogenic defect of irradiated rings (data not shown), consistent with the absence of induction of P16 protein in irradiated HUVEC.

Neg (Lack) Gene_expression (Lack) of p16

6) Confidence 0.56 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2884035 Disease Relevance 0.14 Pain Relevance 0

This gene (also known as p15Ink4b) lies adjacent to the tumor suppressor gene CDKN2A and encodes a cyclin-dependent kinase.

Gene_expression (lies) of CDKN2A associated with cancer

7) Confidence 0.51 Published 2010 Journal PLoS Genetics Section Body Doc Link PMC2883590 Disease Relevance 0.54 Pain Relevance 0

Further, while expression of p19 was variably decreased in lungs from CCSPrtTA/tetO-Sox17 mice maintained on Dox for 2 days, no differences in the expression of p16 or p27 were observed after expression of Sox17 for 1–3 days (data not shown).

Gene_expression (expression) of p16 in lungs

8) Confidence 0.40 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2682659 Disease Relevance 0 Pain Relevance 0

Silencing of p19ARF, an upstream regulator of p53, facilitates reprogramming as well [105].

Gene_expression (Silencing) of p19ARF

9) Confidence 0.32 Published 2011 Journal Journal of Oncology Section Body Doc Link PMC3010739 Disease Relevance 0.83 Pain Relevance 0

Genetic alterations such as the p16(INK4a) deletion, melanocortin 1 receptor (MC1R), RAS, and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) may be indicative of a predisposition to melanoma development.

Gene_expression (deletion) of p16 associated with sarcoma, melanocortin 1 receptor and skin cancer

10) Confidence 0.28 Published 2007 Journal Mol. Carcinog. Section Abstract Doc Link 17570501 Disease Relevance 0.80 Pain Relevance 0.10

However, over-expression of Tert in the background of enhanced cancer resistance (enhanced expression of p53, p16 and p19ARF) increased lifespan in Sp53/Sp16/SArf/TgTert transgenic mice [50].

Gene_expression (expression) of p19ARF associated with targeted disruption, aging and cancer

11) Confidence 0.26 Published 2011 Journal Philosophical Transactions of the Royal Society B: Biological Sciences Section Body Doc Link PMC3001304 Disease Relevance 0.78 Pain Relevance 0.07

However, over-expression of Tert in the background of enhanced cancer resistance (enhanced expression of p53, p16 and p19ARF) increased lifespan in Sp53/Sp16/SArf/TgTert transgenic mice [50].

Gene_expression (expression) of p16 associated with targeted disruption, aging and cancer

12) Confidence 0.26 Published 2011 Journal Philosophical Transactions of the Royal Society B: Biological Sciences Section Body Doc Link PMC3001304 Disease Relevance 0.78 Pain Relevance 0.07

Melan-a cells are functionally Ink4a-Arf null, expressing neither p16INK4A nor ARF proteins (Sviderskaya et al., 2002).

Gene_expression (null) of Ink4a-Arf

13) Confidence 0.21 Published 2009 Journal Pigment Cell & Melanoma Research Section Body Doc Link PMC2784899 Disease Relevance 0.15 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].

Gene_expression (expression) of p16ink4a associated with cancer

14) Confidence 0.14 Published 2011 Journal Journal of Biomedicine and Biotechnology Section Body Doc Link PMC3004414 Disease Relevance 0.51 Pain Relevance 0

Other molecules that have been demonstrated to play a role in arthritis using gene transfer in various in vitro or animal models are Csk, cathepsin L, fibronectin, galectin-1, p16INK4A, p21Cip1, SOCS3, soluble CR1, superoxide dismutase and catalase, Ras, and prothymosin ?

Gene_expression (fibronectin) of p16INK4A associated with arthritis

15) Confidence 0.12 Published 2008 Journal Mod Rheumatol Section Body Doc Link PMC2275302 Disease Relevance 0.78 Pain Relevance 0.29

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