INT184477

Context Info Confidence 0.59 First Reported 2005 Last Reported 2011 Negated 0 Speculated 1 Reported most in Body Documents 27 Total Number 29 Disease Relevance 15.61 Pain Relevance 2.80

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

Anatomy Link Frequency DA neurons 2 brain 2 neurons 2 muscle 1 skeletal muscle 1 Pten (Mus musculus)

Pain Link Frequency Relevance Heat Dopamine 920 99.84 rheumatoid arthritis 52 99.84 dopamine receptor 24 96.68 agonist 22 95.56 Potency 54 94.56 Ventral tegmentum 64 92.04 Substantia nigra 64 91.72 Dynorphin 48 85.52 addiction 12 71.48 cerebral cortex 8 70.32

Disease Link Frequency Relevance Heat Cancer 876 100.00 Rheumatoid Arthritis 52 99.84 Adenocarcinoma 182 99.20 Prostate Cancer 101 99.12 Brain Tumor 128 99.04 Disease 123 98.54 Targeted Disruption 183 98.48 Apoptosis 250 97.76 Glioblastoma 53 96.28 Glioma 100 94.92

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

PTEN downregulation in cultured hippocampal neurons inhibits the release of cytochrome c during toxic insults [41].

Negative_regulation (downregulation) of PTEN in neurons

1) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.23 Pain Relevance 0.31

The continuous and intermittent models were used in case the loss of PTEN resulted in a prolonged signal for muscle growth that was obscured in the continuous overload paradigm.

Negative_regulation (loss) of PTEN in muscle

2) Confidence 0.52 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.23 Pain Relevance 0

Conditional loss of Pten in the brain can have differing consequences depending on the cell type or state of differentiation.

Negative_regulation (loss) of Pten in brain

3) Confidence 0.51 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.75 Pain Relevance 0.07

Disruption of PTEN activity in DA neurons during postmitotic developmental growth

Negative_regulation (Disruption) of PTEN in DA neurons associated with dopamine

4) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.43 Pain Relevance 0.45

A common phenotype associated with the loss of PTEN in neuronal populations is an enlargement of neuronal soma size, increased cell proliferation, inhibition of apoptosis, and the expression of thickened axonal and dendritic processes.

Negative_regulation (loss) of PTEN in neuronal associated with apoptosis

5) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.17 Pain Relevance 0.40

In addition, PTEN inactivation protected DA neurons and significantly enhanced DA-dependent behavioral functions in KO mice after a progressive 6OHDA lesion.

Negative_regulation (inactivation) of PTEN in DA neurons associated with dopamine

6) Confidence 0.43 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2736587 Disease Relevance 0.13 Pain Relevance 0.43

Of the offspring generated, we used Pten loxP/loxP/Cre/wt as knockouts (KO) and Pten wt/wt/Cre/wt as experimental controls.

Negative_regulation (used) of Pten

7) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.10 Pain Relevance 0.08

In KO animals the loss of PTEN immunoreactivity in the ventral mesencephalon was associated with increased TH and phospho-AKT staining (Figure 1B).

Negative_regulation (loss) of PTEN in ventral

8) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.37 Pain Relevance 0.15

However, loss of PTEN in striated muscle does not lead to transformation [22], [23].

Negative_regulation (loss) of PTEN in striated muscle

9) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.32 Pain Relevance 0

In many instances loss of PTEN leads to enhanced tumour formation [30].

Negative_regulation (loss) of PTEN associated with cancer

10) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.31 Pain Relevance 0

The absence of PI3K activation together with the requirement for PI(3,4,5,)P3 observed by Sakamoto suggested that inactivation of PTEN [51] could be important in contraction mediated PKB activation.

Negative_regulation (inactivation) of PTEN

11) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.08 Pain Relevance 0

Since PI3K was not activated following resistance exercise, we next sought to determine whether this pathway was increased due to inactivation of the 3-phosphatase PTEN.

Spec (whether) Negative_regulation (inactivation) of PTEN

12) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.06 Pain Relevance 0

In summary, loss of PTEN in skeletal muscle leads to an increase in the mass of selected muscles during development.

Negative_regulation (loss) of PTEN in skeletal muscle

13) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.23 Pain Relevance 0

In this study, we used Cre-loxP technology to specifically inactivate Pten in dopamine (DA) neurons (Pten KO mice).

Negative_regulation (inactivate) of Pten in neurons associated with dopamine

14) Confidence 0.38 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2736587 Disease Relevance 0.18 Pain Relevance 0.28

In contrast, the loss of PTEN function is an early event in endometrial tumorigenesis.

Negative_regulation (loss) of PTEN

15) Confidence 0.36 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2852605 Disease Relevance 1.59 Pain Relevance 0

PTEN inactivation is induced by mutations that lead to a loss of expression and is induced to a lesser extent by a loss of heterozygosity.

Negative_regulation (inactivation) of PTEN

16) Confidence 0.36 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2852605 Disease Relevance 0.74 Pain Relevance 0

This agrees with the reduction of PTEN

Negative_regulation (reduction) of PTEN

17) Confidence 0.34 Published 2008 Journal PPAR Research Section Body Doc Link PMC2430014 Disease Relevance 0.61 Pain Relevance 0.08

Several previous reports have demonstrated a decrease in insulin sensitivity following loss of PTEN [23], [28].

Negative_regulation (loss) of PTEN

18) Confidence 0.33 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.51 Pain Relevance 0

Interestingly, PTEN is critical in restricting neural stem cell self-renewal and proliferation similar to p53 [119, 120], and the combined loss of p53 and PTEN promotes a synergistic increase in neural stem cell self-renewal associated with elevated levels of c-Myc and rapid growth of gliomas in vivo [27, 121].

Negative_regulation (loss) of PTEN in stem cell associated with glioma

19) Confidence 0.33 Published 2011 Journal Journal of Oncology Section Body Doc Link PMC3010739 Disease Relevance 0.99 Pain Relevance 0.03

As mentioned, loss of the tumor suppressor PTEN is a frequent event in brain tumors [28].

Negative_regulation (loss) of PTEN in brain associated with cancer and brain tumor

20) Confidence 0.33 Published 2011 Journal Journal of Oncology Section Body Doc Link PMC3010739 Disease Relevance 0.90 Pain Relevance 0.03

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