INT254666

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Context Info
Confidence 0.56
First Reported 2008
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 37
Total Number 38
Disease Relevance 23.85
Pain Relevance 1.35

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cytosol (Map2k2) kinase activity (Map2k2)
Anatomy Link Frequency
epithelial cells 8
IEC-6 6
colon 4
liver 1
fibroblast 1
Map2k2 (Mus musculus)
Pain Link Frequency Relevance Heat
metalloproteinase 245 98.44 Very High Very High Very High
Inflammation 29 97.96 Very High Very High Very High
cytokine 32 96.76 Very High Very High Very High
rheumatoid arthritis 74 91.52 High High
Kinase C 1 83.28 Quite High
fibrosis 1 77.20 Quite High
Nerve growth factor 1 50.08 Quite High
Perioperative pain 35 5.00 Very Low Very Low Very Low
isoflurane 35 5.00 Very Low Very Low Very Low
spinal inflammation 10 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Colon Cancer 1575 99.84 Very High Very High Very High
Cancer 1264 99.76 Very High Very High Very High
Adenocarcinoma 280 99.36 Very High Very High Very High
Apoptosis 358 98.76 Very High Very High Very High
Intestinal Cancer 280 98.60 Very High Very High Very High
Arthritis 12 97.96 Very High Very High Very High
Metastasis 350 96.40 Very High Very High Very High
Adhesions 74 94.44 High High
Rheumatoid Arthritis 74 91.52 High High
Stress 37 91.32 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Together, these data demonstrate that constitutive activation of MEK1 or MEK2 is sufficient to transform intestinal epithelial cells and induce the formation of invasive colon adenocarcinomas.


Positive_regulation (activation) of MEK2 in colon associated with adenocarcinoma
1) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.93 Pain Relevance 0
In contrast, expression of activated MEK1 or MEK2 led to drastic morphological changes accompanied by loss of cell-cell contacts; the cells adopted a spindle-like fibroblast morphology, were more refractile and formed multilayers.
Positive_regulation (activated) of MEK2 in fibroblast
2) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.22 Pain Relevance 0
Constitutive activation of MEK1 or MEK2 protects intestinal epithelial cells against anoikis
Positive_regulation (activation) of MEK2 in epithelial cells
3) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.63 Pain Relevance 0.04
No major difference was observed in the growth rate of tumors expressing activated MEK1 or MEK2 (Fig. 2D).
Positive_regulation (activated) of MEK2 associated with cancer
4) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.57 Pain Relevance 0
MEK1 or MEK2 activation had no significant effect on the expression of the pro-apoptotic proteins Bax and Bak in these cells (data not shown).


Positive_regulation (activation) of MEK2 associated with apoptosis
5) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.65 Pain Relevance 0
These observations indicate that constitutive activation of either MEK1 or MEK2 is sufficient to confer a metastatic phenotype to intestinal tumor cells.
Positive_regulation (activation) of MEK2 associated with intestinal cancer
6) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.52 Pain Relevance 0
We examined the impact of MEK1 or MEK2 activation on the motility of IEC-6 cells using two different cell migration assays.
Spec (examined) Positive_regulation (activation) of MEK2 in IEC-6
7) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.68 Pain Relevance 0
As expected, substitution of the activation loop Ser phosphorylation sites by Asp residues strongly potentiated the enzymatic activity of MEK1 and MEK2, but no reproducible difference in activity was observed between the two isoforms (Fig. 1C).
Positive_regulation (potentiated) of MEK2
8) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.37 Pain Relevance 0
However, activation of either MEK1 or MEK2 markedly up-regulated the expression of MMP-13 protein (Fig. 4A).
Positive_regulation (activation) of MEK2
9) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.20 Pain Relevance 0.20
Constitutive activation of MEK1 or MEK2 resulted in the up-regulation of the pro-survival proteins Mcl-1, Bcl-2 and, to a lesser extent, Bcl-xL in IEC-6 cells (Fig. 5B).
Positive_regulation (activation) of MEK2 in IEC-6
10) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.83 Pain Relevance 0
To further extend our investigation to non-colorectal carcinomas, we tested the effect of MEK1 and MEK2 shRNAs on the human breast adenocarcinoma cell line MDA-MB-231, which exhibit strong constitutive activation of MEK1/MEK2 signaling (Fig. 6A).
Positive_regulation (activation) of MEK2 in MDA-MB-231 associated with adenocarcinoma and colon cancer
11) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.34 Pain Relevance 0
Several human colon carcinoma cell lines display constitutive phosphorylation of ERK1/ERK2 MAP kinases [20], likely resulting from activation of MEK1/MEK2.
Positive_regulation (activation) of MEK2 in colon associated with colon cancer
12) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.50 Pain Relevance 0
Quantitative PCR analysis confirmed that constitutive activation of MEK1 or MEK2 induces the expression of urokinase receptor mRNA (Fig. 4B).
Positive_regulation (activation) of MEK2
13) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.07 Pain Relevance 0.18
Constitutive activation of MEK1 or MEK2 confers metastatic properties to transformed intestinal epithelial cells
Positive_regulation (activation) of MEK2 in epithelial cells
14) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.79 Pain Relevance 0
The results presented above clearly demonstrate that constitutive activation of either MEK isoform, MEK1 or MEK2, is sufficient to fully transform intestinal epithelial cells to the metastatic stage.
Positive_regulation (activation) of MEK2 in epithelial cells
15) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.63 Pain Relevance 0
To assess the functional significance of MEK1/MEK2 activation in colorectal cancer, we ectopically expressed wild type and constitutively active (DD mutant) versions of MEK1 and MEK2 by retroviral gene transfer in the normal undifferentiated intestinal epithelial cell line IEC-6 [27].
Positive_regulation (activation) of MEK2 in IEC-6 associated with colon cancer
16) Confidence 0.56 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.45 Pain Relevance 0
The activation levels of ERK, the p38 target MK-2 and the JNK target c-jun in cell lysates were assessed by immunoblotting with phospho-specific antibodies.
Positive_regulation (activation) of MK-2
17) Confidence 0.45 Published 2010 Journal BMC Microbiol Section Body Doc Link PMC3022711 Disease Relevance 0.07 Pain Relevance 0
Studies using RNA interference have suggested that both MEK1 and MEK2 are required for in vitro cell proliferation, and that they contribute to distinct cell cycle regulatory events [25].
Positive_regulation (required) of MEK2
18) Confidence 0.40 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.88 Pain Relevance 0
Of the 69 gene transcripts that showed altered expression in the study of Komatsu, 18 (26%) were found to be modulated in IEC-6 cells expressing constitutively active MEK1 or MEK2.
Positive_regulation (active) of MEK2 in IEC-6
19) Confidence 0.40 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.43 Pain Relevance 0.07
To assess the individual roles of MEK1 and MEK2, we expressed short-hairpin (sh) RNAs specifically targeting MEK1 or MEK2 gene in HCT116 cells using VSV-pseudotyped lentiviral vectors.
Positive_regulation (targeting) of MEK2
20) Confidence 0.40 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2596176 Disease Relevance 0.44 Pain Relevance 0

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