INT151171

Context Info Confidence 0.55 First Reported 2008 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 20 Total Number 20 Disease Relevance 13.30 Pain Relevance 3.54

phosphatase activity (Pten) mitochondrion (Pten) plasma membrane (Pten) nucleus (Pten) intracellular (Pten) enzyme binding (Pten)

Anatomy Link Frequency aortas 2 DA neurons 1 brain 1 striatum 1 dopamine neurons 1 Pten (Mus musculus)

Pain Link Frequency Relevance Heat Clonidine 9 99.98 Dopamine 690 99.66 midbrain 90 98.80 Substantia nigra 49 96.12 Eae 42 93.12 Dynorphin 36 93.12 Inflammation 171 91.48 agonist 68 90.56 Enkephalin 12 88.00 Nicotine 6 85.36

Disease Link Frequency Relevance Heat Diabetes Mellitus 31 99.84 Targeted Disruption 133 99.80 Apoptosis 107 98.60 Cancer 602 98.50 Death 62 98.40 Autism 10 98.32 Lung Cancer 53 97.16 Dna Damage 1 96.28 Thyroid Neoplasm 6 96.08 Cognitive Disorder 6 95.20

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The expression level of clonidine-induced phosphorylated PTEN (phosphatase and tensin homolog deleted on chromosome ten) was significantly increased in diabetic aortas, but chronic simvastatin did not affect it.

Positive_regulation (induced) of PTEN in aortas associated with diabetes mellitus and clonidine

1) Confidence 0.55 Published 2008 Journal J. Pharmacol. Sci. Section Abstract Doc Link 18391484 Disease Relevance 0.91 Pain Relevance 0.35

To further examine the correlation between PTEN and the dopaminergic system, we developed a mouse transgenic model to inactivate PTEN signaling specifically in DA neurons.

Positive_regulation (inactivate) of PTEN in DA neurons associated with targeted disruption and dopamine

2) Confidence 0.50 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.30 Pain Relevance 0.56

For example, the continuous activation of the downstream PTEN pathway, Akt, in mesostriatal adult dopamine neurons by unilateral adenoviral injections in the substantia nigra compacta confers almost complete protection against apoptotic cell death in a dopamine toxin specific model [12].

Positive_regulation (activation) of PTEN in dopamine neurons associated with dopamine, substantia nigra, apoptosis and death

3) Confidence 0.47 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.53 Pain Relevance 0.40

Despite the robust trophic effects accompanied by a significant increase in overall striatal DA tissue content, extracellular DA levels in the striatum remained unchanged between control and Pten KO mice, and potassium evoked DA release was not elevated in Pten KO animals.

Neg (not) Positive_regulation (elevated) of Pten in striatum associated with dopamine

4) Confidence 0.44 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.29 Pain Relevance 0.50

In addition, striatal TH density levels were significantly elevated in Pten KO animals as compared to controls.

Positive_regulation (elevated) of Pten

5) Confidence 0.44 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.43 Pain Relevance 0.25

BDNF messenger levels were significantly increased in Pten KO animals (Fig. 5C).

Positive_regulation (increased) of Pten

6) Confidence 0.44 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0 Pain Relevance 0.76

PTEN is widely distributed in the brain and is preferentially expressed in neurons, where it localizes to both the nucleus and cytoplasm [4]–[7].

Positive_regulation (distributed) of PTEN in neurons

7) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 1.19 Pain Relevance 0

Another group which reported overall changes in brain volume in a genetic mouse line that was haploinsufficient for PTEN and SLC6A4, two susceptibility genes for autism which have an indirect influence on serotonergic signaling, reported sex specific changes in the social approach test (Page et al., 2009).

Positive_regulation (haploinsufficient) of PTEN in brain associated with autism

8) Confidence 0.40 Published 2010 Journal Frontiers in Behavioral Neuroscience Section Body Doc Link PMC2987632 Disease Relevance 0.58 Pain Relevance 0.03

In addition, the upregulation of proapoptotic mechanisms involving AKT-dependent mechanisms is mediated through PTEN, as is the downregulation of anti-apoptotic mechanisms through Bcl-2 [29–31].

Positive_regulation (mediated) of PTEN associated with apoptosis

9) Confidence 0.39 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2852605 Disease Relevance 0.84 Pain Relevance 0

In addition, the upregulation of proapoptotic mechanisms involving AKT-dependent mechanisms is mediated through PTEN, as is the downregulation of anti-apoptotic mechanisms through Bcl-2 [29–31].

Positive_regulation (upregulation) of PTEN associated with apoptosis

10) Confidence 0.39 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2852605 Disease Relevance 0.91 Pain Relevance 0

The expression level of clonidine-induced phosphorylated PTEN (phosphatase and tensin homolog deleted on chromosome ten) was significantly increased in diabetic aortas, but chronic simvastatin did not affect it.

Positive_regulation (increased) of PTEN in aortas associated with diabetes mellitus and clonidine

11) Confidence 0.37 Published 2008 Journal J. Pharmacol. Sci. Section Abstract Doc Link 18391484 Disease Relevance 0.91 Pain Relevance 0.35

Muscle specific knockout of PTEN resulted in small but significant increases in heart (PTEN+/+ ?

Positive_regulation (increases) of PTEN in heart associated with targeted disruption

12) Confidence 0.36 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2905373 Disease Relevance 0.42 Pain Relevance 0

PTEN further acts in opposition to PI3K to control levels of phosphorylated AKT [23, 32].

Positive_regulation (acts) of PTEN

13) Confidence 0.34 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2852605 Disease Relevance 0.86 Pain Relevance 0

Since inactivation of BRCA1 [25] and PTEN [26–28] also increases stem cell

Positive_regulation (inactivation) of PTEN in stem cell

14) Confidence 0.26 Published 2008 Journal PPAR Research Section Body Doc Link PMC2430014 Disease Relevance 0.53 Pain Relevance 0.04

Mechanisms of resistance in specific tumors could involve activation of insulin-like growth factor (IGF)-1 signaling, activation of Met signaling, loss of PTEN, or mutation of K-Ras that can compensate for the therapeutic inhibition of EGFR signaling.

Positive_regulation (activation) of PTEN associated with cancer

15) Confidence 0.24 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2716529 Disease Relevance 0.84 Pain Relevance 0

Increased expression/activity of PTEN would be anticipated to inhibit

Positive_regulation (Increased) of PTEN

16) Confidence 0.19 Published 2008 Journal PPAR Research Section Body Doc Link PMC2396386 Disease Relevance 0.72 Pain Relevance 0.04

Our results further suggest that PKB activity lacked significant association with its antagonistic regulator PTEN as well as with downstream PKB substrates including GSK3?

Positive_regulation (regulator) of PTEN

17) Confidence 0.18 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2270852 Disease Relevance 0.71 Pain Relevance 0

This was at least partially due to upregulation of PTEN and inhibition of Akt activity, which antagonized IGF-1 effects necessary for the progression of thyroid cancers [199].

Positive_regulation (upregulation) of PTEN in thyroid associated with thyroid neoplasm

18) Confidence 0.18 Published 2008 Journal PPAR Research Section Body Doc Link PMC2606065 Disease Relevance 1.06 Pain Relevance 0.11

-dependent upregulation of PTEN and inhibition of Akt activity, and also via PPAR?

Positive_regulation (ent upregula) of PTEN

19) Confidence 0.18 Published 2008 Journal PPAR Research Section Body Doc Link PMC2606065 Disease Relevance 0.64 Pain Relevance 0.14

This can stimulate autophagy by activating AMPK or by upregulating phosphatase and tensin homologue (PTEN, a PIP3 3?

Positive_regulation (upregulating) of PTEN

20) Confidence 0.14 Published 2010 Journal Seminars in Cell & Developmental Biology Section Body Doc Link PMC2938570 Disease Relevance 0.63 Pain Relevance 0

General Comments

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