INT119834

Context Info Confidence 0.79 First Reported 2004 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 12 Total Number 12 Disease Relevance 6.78 Pain Relevance 0.75

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

Anatomy Link Frequency SK-N-SH 2 colon 1 PTEN (Homo sapiens)

Pain Link Frequency Relevance Heat cINOD 11 99.48 ischemia 3 80.08 cytokine 14 79.92 COX-2 inhibitor 1 79.28 Restless leg syndrome 3 63.56 cva 4 5.72 Inflammation 36 5.00 Central nervous system 22 5.00 chemokine 5 5.00 corticosteroid 3 5.00

Disease Link Frequency Relevance Heat Apoptosis 87 99.80 Endometrial Cancer 60 99.60 Death 17 99.20 Cancer 287 98.92 Neuroblastoma 3 98.38 Colon Cancer 12 97.24 Skin Cancer 63 95.84 Monosomy 20 94.56 Melanoma 91 91.44 Mantle-cell Lymphoma 33 90.92

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

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

Phosphorylation (phosphatase) of PTEN associated with cancer

1) Confidence 0.79 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886332 Disease Relevance 0.54 Pain Relevance 0

Phosphatase and tensin homolog (PTEN) is one of the identified tumor suppressor genes, located on 10q23, with strong evidence for a role in CM tumorigenesis [92] (Table 2).

Phosphorylation (Phosphatase) of PTEN associated with cancer and skin cancer

2) Confidence 0.74 Published 2010 Journal Dermatology Research and Practice Section Body Doc Link PMC2902045 Disease Relevance 1.94 Pain Relevance 0

However, resistance to trastuzumab is frequent [6] and its mechanisms are poorly understood [7], although ERBB2 phosphorylation [8], PTEN and PIK3CA status [9] seem important factors.

Phosphorylation (phosphorylation) of PTEN

3) Confidence 0.61 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2958950 Disease Relevance 0.20 Pain Relevance 0

PTEN dephosphorylates PIP3 into inactive PIP2, which blocks Akt activation.

Phosphorylation (dephosphorylates) of PTEN

4) Confidence 0.58 Published 2004 Journal Mol Cancer Section Body Doc Link PMC394342 Disease Relevance 0.69 Pain Relevance 0.03

B phosphorylation in mutated PTEN RL 95-2 and Ishikawa cells (Fig. 2).

Phosphorylation (phosphorylation) of PTEN

5) Confidence 0.58 Published 2004 Journal Mol Cancer Section Body Doc Link PMC394342 Disease Relevance 0.38 Pain Relevance 0

PTEN is a crucial phosphatase involved in the regulation of Akt phosphorylation: the presence of an active PTEN protein blocks Akt phosphorylation by the dephosphorylation of PI 3-K product, PIP3 [45].

Phosphorylation (phosphorylation) of PTEN

6) Confidence 0.58 Published 2004 Journal Mol Cancer Section Body Doc Link PMC394342 Disease Relevance 0.29 Pain Relevance 0.04

Cilostazol suppressed TNF-alpha-induced decrease in viability of SK-N-SH (human neuroblastoma) cells and HCN-1A (human cortical neuron) cells in association with decrease in PTEN phosphorylation and increase in Akt/CREB phosphorylation with suppression of DNA fragmentation, all of which were antagonized by iberiotoxin, a maxi-K(+) channel blocker.

Phosphorylation (phosphorylation) of PTEN in SK-N-SH associated with neuroblastoma

7) Confidence 0.58 Published 2006 Journal Curr. Pharm. Des. Section Abstract Doc Link 16472148 Disease Relevance 0.62 Pain Relevance 0.10

Thus, it was suggested that the action of cilostazol to promote cell survival was ascribed to the maxi-K channel opening-coupled upregulation of CK2 phosphorylation and downregulation of PTEN phosphorylation with resultant increased phosphorylation of Akt and CREB.

Phosphorylation (phosphorylation) of PTEN

8) Confidence 0.58 Published 2006 Journal Curr. Pharm. Des. Section Abstract Doc Link 16472148 Disease Relevance 0.36 Pain Relevance 0.03

Further, cilostazol prevented TNF-alpha-induced PTEN phosphorylation and apoptotic cell death via increased CK2 phosphorylation in the SK-N-SH cells.

Phosphorylation (phosphorylation) of PTEN in SK-N-SH associated with apoptosis and death

9) Confidence 0.58 Published 2006 Journal Curr. Pharm. Des. Section Abstract Doc Link 16472148 Disease Relevance 0.60 Pain Relevance 0.09

These results suggest that as a consequence of increased expression of phosphatases such as PTEN and the resulting dephosphorylation of kinases, NSAIDs can negatively regulate the EGF/PDGF pathways in colon cancer cells-a novel mechanism for NSAIDs' chemopreventive actions.

Phosphorylation (dephosphorylation) of PTEN in colon associated with colon cancer and cinod

10) Confidence 0.55 Published 2004 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 15240129 Disease Relevance 0.50 Pain Relevance 0.46

Dal et al. demonstrate that the constitutive activation of Akt correlates with the expression of the phosphorylated, inactive form of PTEN.

Neg (inactive) Phosphorylation (phosphorylated) of PTEN

11) Confidence 0.20 Published 2008 Journal J Hematop Section Body Doc Link PMC2713479 Disease Relevance 0.46 Pain Relevance 0

The intracellular mechanism of action of lapatinib, in contrast to the extracellular approach of trastuzumab, results in inhibition the phosphorylation of p95HER2.41 PTEN reduction or deficiency results in increased signaling via the critical PI3K/Akt pathway.

Phosphorylation (phosphorylation) of PTEN

12) Confidence 0.15 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004582 Disease Relevance 0.20 Pain Relevance 0

General Comments

This test has worked.