INT119838

Context Info Confidence 0.67 First Reported 2003 Last Reported 2011 Negated 1 Speculated 0 Reported most in Body Documents 25 Total Number 26 Disease Relevance 21.71 Pain Relevance 2.50

lipid binding (PTEN) cell proliferation (PTEN) cytosol (PTEN) plasma membrane (PTEN) nucleus (PTEN) enzyme binding (PTEN)

Anatomy Link Frequency cleavage 2 colon 1 osteoclast 1 ganglion cells 1 PTEN (Homo sapiens)

Pain Link Frequency Relevance Heat cINOD 32 99.98 rheumatoid arthritis 227 99.12 Arthritis 166 98.96 spinal inflammation 93 98.60 agonist 61 95.12 Inflammation 155 94.16 methotrexate 163 88.64 COX-2 inhibitor 54 84.28 antagonist 49 83.20 cytokine 36 77.20

Disease Link Frequency Relevance Heat Cancer 885 100.00 Endometrial Cancer 502 99.84 Syndrome 76 99.68 Stomach Cancer 7 99.60 Infection 46 99.32 Glioma 10 99.24 Rheumatoid Arthritis 244 99.12 Lung Cancer 57 99.08 Apoptosis 345 98.96 Seronegative Spondarthritis 94 98.96

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Event

Anatomy

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Speculation

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In that regard, Kwak et al. [77] showed that AG-490, an inhibitor of Jak2/Jak3 activity, actually induced osteoclast survival by activating both the MEK/ERK and PI3K/PTEN/Akt cell survival pathway.

Positive_regulation (activating) of PTEN in osteoclast

1) Confidence 0.67 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2842969 Disease Relevance 0.52 Pain Relevance 0.38

NSAIDs activate PTEN and other phosphatases in human colon cancer cells: novel mechanism for chemopreventive action of NSAIDs.

Positive_regulation (activate) of PTEN in colon associated with colon cancer and cinod

2) Confidence 0.60 Published 2004 Journal Biochem. Biophys. Res. Commun. Section Title Doc Link 15240129 Disease Relevance 0.42 Pain Relevance 0.45

A more recent study suggested that diabetic-associated ED due to upregulation of the penile RhoA/Rho-kinase pathway enhances PTEN/Akt activity leading to corporal apoptosis [91].

Positive_regulation (enhances) of PTEN associated with erectile dysfunction, diabetes mellitus and apoptosis

3) Confidence 0.49 Published 2010 Journal Advances in Pharmacological Sciences Section Body Doc Link PMC2997760 Disease Relevance 1.28 Pain Relevance 0

Evaluation of PTEN inactivation in endometrial carcinoma precursor lesions by PTEN immunostaining has been proposed.

Positive_regulation (inactivation) of PTEN associated with endometrial cancer

4) Confidence 0.48 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 1.32 Pain Relevance 0

PTEN (the lipid phosphatase and tensin homolog) is a key tumor suppressor that normally regulates the activation of PI3K.66 The loss of PTEN and mutations in PI3K have been proposed to predict resistance to EGFR inhibitors, however, this is preliminary and no definite conclusions can be derived.64 Conclusions

Positive_regulation (activation) of PTEN associated with cancer

5) Confidence 0.45 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886332 Disease Relevance 0.53 Pain Relevance 0

This immunohistochemical pattern suggests that the large dysplastic ganglion cells (the gangliocytomatous component) forming the greater part of the lesion were associated with activation of the phosphatidylinositol 3-kinase-PTEN/Akt/mTOR signaling pathway, a feature previously reported in LDD.

Positive_regulation (activation) of PTEN in ganglion cells associated with ganglion cysts and disease

6) Confidence 0.45 Published 2007 Journal J. Neurosurg. Section Abstract Doc Link 18459885 Disease Relevance 1.11 Pain Relevance 0.07

PTEN (the lipid phosphatase and tensin homolog) is a key tumor suppressor that normally regulates the activation of PI3K.66 The loss of PTEN and mutations in PI3K have been proposed to predict resistance to EGFR inhibitors, however, this is preliminary and no definite conclusions can be derived.64 Conclusions

Positive_regulation (activation) of PTEN associated with cancer

7) Confidence 0.45 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886332 Disease Relevance 0.60 Pain Relevance 0

was found to inhibit phosphatidylinositol 3-kinase (PI3K)/Akt signaling and retinoblastoma protein (Rb) dephosphorylation [70], induce expression of cyclin D1 [71] and Bcl-xl/Bcl-2 [72], upregulate p21 and p27 [73–75], interact with XIAP [76], upregulate PTEN [77], and enhance the sensitivity of tumor cells to tumor necrosis factor-related apoptosis-inducing ligand- (TRAIL-) induced cell death [78].

Positive_regulation (upregulate) of PTEN associated with necrosis, cancer, apoptosis, retinoblastoma and death

8) Confidence 0.45 Published 2009 Journal PPAR Research Section Body Doc Link PMC2770108 Disease Relevance 1.76 Pain Relevance 0.03

Recently, interactions between the PI3K/AKT and p53 signaling pathways have been described in which activation of the PI3K/AKT pathway through PTEN or PIK3CA mutations, together with p53 inactivation, results in malignant transformation [15].

Positive_regulation (activation) of PTEN associated with malignant neoplastic disease

9) Confidence 0.45 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 0.61 Pain Relevance 0

Some investigators have claimed that PIK3CA mutations are mutually exclusive of PTEN mutations, suggesting that tumorigenic signaling through this pathway can occur either through activation of PIK3CA or inactivation of PTEN [9].

Positive_regulation (activation) of PTEN

10) Confidence 0.45 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 0.52 Pain Relevance 0

PTEN is a major tumor suppressor gene that is inactivated in 50% of high-grade gliomas (5).

Positive_regulation (inactivated) of PTEN associated with cancer and glioma

11) Confidence 0.44 Published 2010 Journal Brain Pathology (Zurich, Switzerland) Section Body Doc Link PMC2991767 Disease Relevance 1.54 Pain Relevance 0.04

It has been shown that NS-398 was able to increase the level of PTEN in human gastric carcinoma cell line MKN45 [114].

Positive_regulation (increase) of PTEN associated with stomach cancer

12) Confidence 0.36 Published 2010 Journal International Journal of Cell Biology Section Body Doc Link PMC2841246 Disease Relevance 0.99 Pain Relevance 0.03

These results demonstrate that the ability of PTEN to negatively regulate the PI 3-K/Akt/NF-?

Positive_regulation (ability) of PTEN

13) Confidence 0.36 Published 2004 Journal Mol Cancer Section Body Doc Link PMC394342 Disease Relevance 0.23 Pain Relevance 0

of IkB, induction of TSC22, NF-kB, GADD153, PTEN, etc.) may depend on the

Positive_regulation (induction) of PTEN

14) Confidence 0.34 Published 2008 Journal PPAR Research Section Body Doc Link PMC2464819 Disease Relevance 0.79 Pain Relevance 0

We have demonstrated previously that Akt is constitutively phosphorylated/activated in two mutated-PTEN human endometrial cancer cell lines that have been used in the present study (RL 95-2 and Ishikawa) [32,42].

Positive_regulation (activated) of mutated-PTEN associated with endometrial cancer

15) Confidence 0.31 Published 2004 Journal Mol Cancer Section Body Doc Link PMC394342 Disease Relevance 0.29 Pain Relevance 0.03

associated with synergistic upregulation of PTEN expression [49].

Positive_regulation (upregulation) of PTEN

16) Confidence 0.31 Published 2008 Journal PPAR Research Section Body Doc Link PMC2408709 Disease Relevance 1.10 Pain Relevance 0.12

of Akt, an upstream positive modulator of mTOR, and to increase PTEN, a

Positive_regulation (increase) of PTEN

17) Confidence 0.21 Published 2008 Journal PPAR Research Section Body Doc Link PMC2515882 Disease Relevance 0.52 Pain Relevance 0.04

TZDs induced upregulation of PTEN and p21, downregulation of cyclins D and E, and

Positive_regulation (upregulation) of PTEN

18) Confidence 0.19 Published 2008 Journal PPAR Research Section Body Doc Link PMC2528242 Disease Relevance 1.37 Pain Relevance 0.12

Somatic mutation of PTEN was also demonstrated in some cases of vulvar SCC and VIN, suggesting that PTEN mutation possibly played a role early in the carcinogenesis of vulvar SCC [37].

Positive_regulation (mutation) of PTEN associated with cancer and basal and squamous cell skin cancer

19) Confidence 0.18 Published 2011 Journal Journal of Skin Cancer Section Body Doc Link PMC3003991 Disease Relevance 2.52 Pain Relevance 0

Despite documented HER2 receptor amplification, patients may have de novo or acquired resistance to trastuzumab. 39 Potential mechanisms of trastuzumab resistance include altered receptor–antibody interaction (MUC4, p95HER2, ErbB2 mutations), altered downstream signaling (reduced p27, reduced PTEN, activation of PI3K, activation of Akt) and crosstalk with other signaling pathways (IGF-R1, ER, VEGFR).40 The p95HER2 receptor is created either by cleavage and shedding of the extracellular domain of the HER2 receptor or by specific mRNA splicing, resulting in a constitutively active truncated receptor which is associated with a more aggressive phenotype.

Positive_regulation (activation) of PTEN in cleavage

20) Confidence 0.16 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004582 Disease Relevance 0.26 Pain Relevance 0

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