INT200670

Context Info Confidence 0.75 First Reported 2006 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 25 Total Number 26 Disease Relevance 16.25 Pain Relevance 3.00

nucleoplasm (AKT2) transport (AKT2) mitochondrion (AKT2) carbohydrate metabolic process (AKT2) cytoplasm (AKT2) cytosol (AKT2)

Anatomy Link Frequency HeLa 3 liver 1 skeletal muscle 1 apoptotic cell 1 epithelial cells 1 AKT2 (Homo sapiens) AKT2 - D399N (2) AKT2 - D32H (1)

Pain Link Frequency Relevance Heat cytokine 23 100.00 chemokine 2 100.00 Brush evoked pain 60 98.48 cerebral cortex 3 98.44 rheumatoid arthritis 96 97.30 intrathecal 42 96.72 Peripheral nerve injury 15 96.68 Spinal cord 33 96.32 Stimulus evoked pain 6 93.52 Neuropathic pain 45 91.52

Disease Link Frequency Relevance Heat Endometrial Cancer 459 100.00 Apoptosis 725 99.52 Cervical Cancer 80 99.42 Neuropathic Pain 111 98.48 Death 408 97.88 Cancer 883 97.78 Hyperplasia 58 97.32 Rheumatoid Arthritis 96 97.30 Shock 1 96.52 Nervous System Injury 51 96.24

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

/Akt2 expression on the phosphorylation of GSK3?

Gene_expression (expression) of Akt2

1) Confidence 0.75 Published 2010 Journal BMC Dev Biol Section Body Doc Link PMC2910663 Disease Relevance 0 Pain Relevance 0

We used the PDGF-BB isoform in all experiments in this study because PDGF-B chain expression is induced after peripheral nerve injury [25], neurons throughout the CNS contain the PDGF-B chain [26], and the PDGF-B chain activates both PDGFR?

Gene_expression (isoform) of -BB in neurons associated with nervous system injury and peripheral nerve injury

2) Confidence 0.65 Published 2009 Journal Mol Pain Section Body Doc Link PMC2690582 Disease Relevance 0.81 Pain Relevance 0.87

l, as a vehicle control) was intrathecally administered 30 min before PDGF-BB (10 pmol/10 ?

Gene_expression (administered) of -BB

3) Confidence 0.65 Published 2009 Journal Mol Pain Section Body Doc Link PMC2690582 Disease Relevance 0.22 Pain Relevance 0.47

Furthermore, applying PDGF-BB (50 ng/ml) to primary cultured microglial cells enhanced the immunofluorescence for p-PDGFR?

Gene_expression (applying) of -BB in microglial cells

4) Confidence 0.65 Published 2009 Journal Mol Pain Section Body Doc Link PMC2690582 Disease Relevance 0.08 Pain Relevance 0.35

However, in the patient, we observed LOH deletion in AKT1, under-expression of AKT2, mTOR, elF4E, and over-expression of the negative regulators eIF4EBP1 and NKX3-1.

Gene_expression (expression) of AKT2

5) Confidence 0.52 Published 2010 Journal Genome Biol Section Body Doc Link PMC2945784 Disease Relevance 0.81 Pain Relevance 0

Our study demonstrated that HDAC inhibitors, such as valproic acid and butyrate, induce apoptosis in HeLa cervical cancer cells by inhibition of gene expression of Akt1 and Akt2.

Gene_expression (expression) of Akt2 in HeLa associated with cervical cancer and apoptosis

6) Confidence 0.51 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1762018 Disease Relevance 1.15 Pain Relevance 0

Treatment of HeLa cells with HDAC inhibitors such as valproic acid and butyrate leads to inhibition of Akt1 and Akt2 expression, consequently to deactivation of cellular Akt (Fig. 1 and 2).

Gene_expression (expression) of Akt2 in HeLa

7) Confidence 0.51 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1762018 Disease Relevance 0.85 Pain Relevance 0

As shown in Fig. 5C, both valproic acid and butyrate decreased the levels of Akt1 and Akt2 mRNA to a certain degree, but not significantly.

Gene_expression (levels) of Akt2 mRNA

8) Confidence 0.51 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1762018 Disease Relevance 0.25 Pain Relevance 0

We, for the first time, show that the down-regulation of Akt activity is a consequence of inhibition of Akt1 and Akt2 expression by valproic acid and butyrate.

Gene_expression (expression) of Akt2

9) Confidence 0.51 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1762018 Disease Relevance 0.65 Pain Relevance 0

Mutations in AKT family members and their correlation with other gene alterations are found in endometrial carcinoma, including AKT2 (D399N), AKT2 (D32H) and AKT3 (E438D) mutations.

Gene_expression (found) of AKT2 (D399N) associated with endometrial cancer

10) Confidence 0.49 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 0.50 Pain Relevance 0

Mutations in AKT family members and their correlation with other gene alterations are found in endometrial carcinoma, including AKT2 (D399N), AKT2 (D32H) and AKT3 (E438D) mutations.

Gene_expression (found) of AKT2 (D32H) associated with endometrial cancer

11) Confidence 0.49 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 0.50 Pain Relevance 0

Mutations in AKT family members and their correlation with other gene alterations are found in endometrial carcinoma, including AKT2 (D399N), AKT2 (D32H) and AKT3 (E438D) mutations.

Gene_expression (mutations) of AKT2 (D399N) associated with endometrial cancer

12) Confidence 0.49 Published 2010 Journal Obstetrics and Gynecology International Section Body Doc Link PMC2846683 Disease Relevance 0.50 Pain Relevance 0

Akt1 is the predominant isoform in most tissues while Akt2 is highly expressed in skeletal muscle, heart, liver and kidney [22,23].

Gene_expression (expressed) of Akt2 in skeletal muscle

13) Confidence 0.44 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1762018 Disease Relevance 0.67 Pain Relevance 0.15

Valproic acid treatment also reduced the levels of the Akt1 and Akt2 mRNA, but to a lesser degree (Fig. 1B).

Gene_expression (levels) of Akt2 mRNA

14) Confidence 0.44 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1762018 Disease Relevance 0.33 Pain Relevance 0

, Akt2/PKB?

Gene_expression (/) of Akt2

15) Confidence 0.44 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1762018 Disease Relevance 0.69 Pain Relevance 0.13

Akt3 is the most abundant of Akt isoforms, about 2 and 4 fold more than Akt1 and Akt2 respectively (Fig. 1C), which is not a normal Akt isoform expression pattern for cervical epithelial cells.

Gene_expression (respectively) of Akt2 in epithelial cells

16) Confidence 0.44 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1762018 Disease Relevance 0.21 Pain Relevance 0

However, in the patient, we observed LOH deletion in AKT1, under-expression of AKT2, mTOR, elF4E, and over-expression of the negative regulators eIF4EBP1 and NKX3-1.

Gene_expression (expression) of AKT2

17) Confidence 0.40 Published 2010 Journal Genome Biol Section Body Doc Link PMC2945784 Disease Relevance 0.81 Pain Relevance 0

As shown in Fig. 1B, following 16 hours of butyrate treatment, the levels of Akt1 and Akt2 mRNA were reduced by about 70% and 50% respectively as compared to untreated control cells.

Gene_expression (levels) of Akt2 mRNA

18) Confidence 0.39 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1762018 Disease Relevance 0.40 Pain Relevance 0

Here we report that the induction of cancer cell apoptosis by HDAC inhibitors, such as valproic acid and butyrate, is achieved through inhibition of gene expression of Akt1 and Akt2, pro-survival factors involved in many cell signalling pathways.

Gene_expression (expression) of Akt2 associated with cancer and apoptosis

19) Confidence 0.39 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1762018 Disease Relevance 1.16 Pain Relevance 0

Taken together, these data suggest that the down-regulation of Akt activity by HDAC inhibitors, such as valproic acid and butyrate, is achieved through inhibition of gene expression of Akt1 and Akt2.

Gene_expression (expression) of Akt2

20) Confidence 0.39 Published 2006 Journal Mol Cancer Section Body Doc Link PMC1762018 Disease Relevance 0.26 Pain Relevance 0

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