INT44478

Context Info Confidence 0.57 First Reported 1984 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 32 Total Number 32 Disease Relevance 27.45 Pain Relevance 0.63

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

Anatomy Link Frequency ovary 1 PTEN (Homo sapiens)

Pain Link Frequency Relevance Heat antagonist 13 98.08 endometriosis 108 97.80 Inflammation 16 88.12 cytokine 10 87.40 tricyclic antidepressant 1 75.00 antidepressant 1 68.12 Nortriptyline 3 62.32 depression 1 61.56 Spinal cord 1 58.12 Desipramine 2 55.84

Disease Link Frequency Relevance Heat Cholesteatoma 60 100.00 Melanoma 290 99.96 Cancer 1658 99.92 Endometrial Cancer 1224 99.84 Endometroid Carcinoma 169 99.84 Hepatocellular Cancer 38 99.60 Glioma 3 99.50 Syndrome 186 99.48 Apoptosis 233 99.08 Skin Cancer 324 98.88

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

Negative_regulation (loss) of PTEN associated with cancer

1) Confidence 0.57 Published 2009 Journal OncoTargets and therapy Section Body Doc Link PMC2886332 Disease Relevance 0.53 Pain Relevance 0

In in vitro studies, cells with PTEN inactivation in endometrioid carcinoma are sensitive to mTOR inhibitors, since the loss of PTEN leads to constitutive activation of downstream components, which in turn up-regulates mTOR activity [62].

Negative_regulation (loss) of PTEN associated with endometroid carcinoma

2) Confidence 0.56 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 0.90 Pain Relevance 0

Lastly, the mutated RB1 may also play a role in the observed erlotinib insensitivity, as the loss of both RB1 and PTEN as seen in this tumor has previously been implicated in gefitinib resistance [36].

Negative_regulation (loss) of PTEN associated with cancer

3) Confidence 0.55 Published 2010 Journal Genome Biol Section Body Doc Link PMC2945784 Disease Relevance 0.78 Pain Relevance 0

PTEN loss has also been implicated in resistance to the EGFR inhibitors gefitinib [34] and erlotinib [35], to which the tumor was determined to be insensitive.

Negative_regulation (loss) of PTEN associated with cancer

4) Confidence 0.55 Published 2010 Journal Genome Biol Section Body Doc Link PMC2945784 Disease Relevance 0.76 Pain Relevance 0

These changes mitigate the effect of PTEN loss on the PI3K/AKT pathway and suggest that the loss of PTEN serves primarily to further activate the RET pathway to drive tumor growth.

Negative_regulation (loss) of PTEN associated with cancer

5) Confidence 0.55 Published 2010 Journal Genome Biol Section Body Doc Link PMC2945784 Disease Relevance 0.85 Pain Relevance 0

These changes mitigate the effect of PTEN loss on the PI3K/AKT pathway and suggest that the loss of PTEN serves primarily to further activate the RET pathway to drive tumor growth.

Negative_regulation (loss) of PTEN associated with cancer

6) Confidence 0.48 Published 2010 Journal Genome Biol Section Body Doc Link PMC2945784 Disease Relevance 0.80 Pain Relevance 0

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

Negative_regulation (inactivation) of PTEN associated with endometrial cancer

7) Confidence 0.41 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 1.32 Pain Relevance 0

In in vitro studies, cells with PTEN inactivation in endometrioid carcinoma are sensitive to mTOR inhibitors, since the loss of PTEN leads to constitutive activation of downstream components, which in turn up-regulates mTOR activity [62].

Negative_regulation (inactivation) of PTEN associated with endometroid carcinoma

8) Confidence 0.41 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 1.03 Pain Relevance 0

Thus, loss of PTEN function leads to increased levels of phospho-AKT, activation of anti-apoptotic protein, and cell cycle progression [9].

Negative_regulation (loss) of PTEN associated with apoptosis

9) Confidence 0.41 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 1.78 Pain Relevance 0

PTEN may be also inactivated by deletion, as shown by LOH in 40% of endometrial carcinomas [7–9, 17].

Negative_regulation (inactivated) of PTEN associated with endometrial cancer

10) Confidence 0.41 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 1.12 Pain Relevance 0

PTEN may be inactivated by several mechanisms such as mutation, LOH, and promoter hypermethylation.

Negative_regulation (inactivated) of PTEN

11) Confidence 0.41 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 0.98 Pain Relevance 0

Human glioma xenografts treated with PTEN/MMAC gene transfer exhibited...[33]

Negative_regulation (exhibited) of PTEN associated with glioma

12) Confidence 0.41 Published 2005 Journal BMC Bioinformatics Section Body Doc Link PMC1090552 Disease Relevance 0.10 Pain Relevance 0

Human glioma xenografts treated with PTEN/MMAC gene transfer exhibited...[33]

Negative_regulation (exhibited) of MMAC associated with glioma

13) Confidence 0.41 Published 2005 Journal BMC Bioinformatics Section Body Doc Link PMC1090552 Disease Relevance 0.10 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].

Negative_regulation (exclusive) of PTEN

14) Confidence 0.41 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 0.46 Pain Relevance 0

Since PTEN mediates crosstalk between PI3K and RET signaling by negatively regulating SHC and ERK [32] and up-regulated RET can also activate the PI3K/AKT pathway [33], loss of PTEN would up-regulate both the PI3K/AKT and RET-MAPK pathways, leading to decreased apoptosis, increased protein synthesis and cellular proliferation.

Negative_regulation (loss) of PTEN associated with apoptosis and hyperplasia

15) Confidence 0.41 Published 2010 Journal Genome Biol Section Body Doc Link PMC2945784 Disease Relevance 0.83 Pain Relevance 0

The actual inactivation of PTEN is observed in up to 30%–40% of CM cell lines [92, 93], but only in 10% of primary CMs.

Negative_regulation (inactivation) of PTEN associated with skin cancer

16) Confidence 0.39 Published 2010 Journal Dermatology Research and Practice Section Body Doc Link PMC2902045 Disease Relevance 1.91 Pain Relevance 0

In UM, inactivation of PTEN is reported in 15% of cases and has been linked to an increase in aneuploidy but also poor clinical outcome [111, 112].

Negative_regulation (inactivation) of PTEN associated with aneuploidy and melanoma

17) Confidence 0.39 Published 2010 Journal Dermatology Research and Practice Section Body Doc Link PMC2902045 Disease Relevance 1.80 Pain Relevance 0

PTEN inactivation or downregulation is mainly found in tumors with an increase in aneuploidy, suggesting that it is a late event in tumor progression [27, 111].

Negative_regulation (downregulation) of PTEN associated with aneuploidy and cancer

18) Confidence 0.39 Published 2010 Journal Dermatology Research and Practice Section Body Doc Link PMC2902045 Disease Relevance 1.86 Pain Relevance 0

As with the TCAs, remember to administer doses of BZs that are reduced by 50 to 75 per cent of the usual recommended doses for young and middle-aged individuals and to increase dosage in small increments.

Negative_regulation (reduced) of BZs

19) Confidence 0.37 Published 1984 Journal Psychiatr. Clin. North Am. Section Abstract Doc Link 6441158 Disease Relevance 0.38 Pain Relevance 0.21

PTEN inactivation by mutation seems to also be involved in tumorigenesis, since it occurs in about 90% of type I carcinomas [11].

Negative_regulation (inactivation) of PTEN associated with carcinoma

20) Confidence 0.36 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 1.98 Pain Relevance 0

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