INT124954

Context Info Confidence 0.75 First Reported 2005 Last Reported 2010 Negated 1 Speculated 1 Reported most in Body Documents 26 Total Number 34 Disease Relevance 15.08 Pain Relevance 3.12

endosome (Egfr) cell morphogenesis (Egfr) intracellular (Egfr) enzyme binding (Egfr) cytoplasm (Egfr) signal transducer activity (Egfr)

Anatomy Link Frequency neurons 7 renal tubule 1 margin 1 brain 1 tongue 1 Egfr (Rattus norvegicus)

Pain Link Frequency Relevance Heat Inflammation 315 99.20 cINOD 34 98.94 Pain 133 95.20 agonist 36 90.40 cytokine 190 80.32 chemokine 40 79.68 interneuron 1 72.48 imagery 147 65.20 depression 6 50.56 COX2 8 25.00

Disease Link Frequency Relevance Heat Cholesteatoma 96 99.96 Apoptosis 36 99.96 Lung Cancer 6 99.92 Cancer 574 99.84 Nociception 198 99.52 Solid Tumor 12 99.32 INFLAMMATION 389 99.20 Ulcers 97 99.20 Colon Cancer 57 98.36 Pruritus 24 98.00

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Anton et al. [23] show that neurons in the cortical plate express erbB receptors and that NRG1 stimulates migration along radial glia.

Gene_expression (express) of erbB in neurons

1) Confidence 0.75 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2965671 Disease Relevance 0 Pain Relevance 0.07

The levels of c-erbB receptor expression by Schwann cells, and the degree to which axons regenerated into the distal stumps both decreased with an increased period of denervation.

Gene_expression (expression) of erbB in Schwann cells

2) Confidence 0.75 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2556676 Disease Relevance 0.25 Pain Relevance 0

Immunohistochemical and Western blot analysis were done to determine COX-2, epidermal growth factor receptor (EGFR), Akt, androgen receptor, and cyclin D1 expression.

Gene_expression (expression) of EGFR

3) Confidence 0.73 Published 2007 Journal Clin. Cancer Res. Section Body Doc Link 17908994 Disease Relevance 0.08 Pain Relevance 0

Immunohistochemical and Western blot analysis were done to determine COX-2, epidermal growth factor receptor (EGFR), Akt, androgen receptor, and cyclin D1 expression.

Gene_expression (expression) of epidermal growth factor receptor

4) Confidence 0.73 Published 2007 Journal Clin. Cancer Res. Section Body Doc Link 17908994 Disease Relevance 0.08 Pain Relevance 0

EGFR is expressed in the basal layer of the epidermis and contributes to the stimulation of epidermal growth, inhibition of differentiation, and acceleration of wound healing.

Gene_expression (expressed) of EGFR in epidermis associated with wound healing

5) Confidence 0.72 Published 2010 Journal Current Oncology Section Body Doc Link PMC2901793 Disease Relevance 1.13 Pain Relevance 0.12

EGFR is overexpressed in a variety of solid tumors, including colorectal cancer (CRC), squamous cell cancer of the head and neck, and non-small-cell lung cancer.

Gene_expression (overexpressed) of EGFR in lung associated with lung cancer, squamous cell neoplasms, colon cancer and solid tumor

6) Confidence 0.72 Published 2010 Journal Current Oncology Section Body Doc Link PMC2901793 Disease Relevance 0.91 Pain Relevance 0

Increased EGFR expression in the ascending loop of Henle, where 70% of filtered magnesium is reabsorbed, may result in damage to the renal tubule and interfere with magnesium transport85,88.

Gene_expression (expression) of EGFR in renal tubule

7) Confidence 0.72 Published 2010 Journal Current Oncology Section Body Doc Link PMC2901793 Disease Relevance 1.14 Pain Relevance 0.03

EGFR overexpression is associated with poorer prognosis in these malignancies10–14 and, in CRC, may be associated with an advanced disease stage15–18.

Gene_expression (overexpression) of EGFR associated with colon cancer and disease

8) Confidence 0.72 Published 2010 Journal Current Oncology Section Body Doc Link PMC2901793 Disease Relevance 0.94 Pain Relevance 0

A strong inhibition of total and phosphorylated form of EGFR (Tyr(992) and Tyr(845)) and Akt (Ser(473)) was significant in rats given with these agents in combination.

Gene_expression (form) of EGFR

9) Confidence 0.63 Published 2007 Journal Clin. Cancer Res. Section Body Doc Link 17908994 Disease Relevance 0.05 Pain Relevance 0

An overall decrease in COX-2, EGFR, Akt, androgen receptor, and cyclin D1 expression was found associated with tumor growth inhibition.

Gene_expression (expression) of EGFR

10) Confidence 0.57 Published 2007 Journal Clin. Cancer Res. Section Body Doc Link 17908994 Disease Relevance 0.06 Pain Relevance 0

Blepharitis, or inflammation of the lid margin, results from inflammation of the meibomian glands, which contain EGFR-expressing cells.

Gene_expression (expressing) of EGFR in meibomian glands associated with disorders of the lacrimal system and inflammation

11) Confidence 0.56 Published 2010 Journal Current Oncology Section Body Doc Link PMC2901793 Disease Relevance 1.57 Pain Relevance 0.10

EGFR is overexpressed in a variety of solid tumors, including colorectal cancer (CRC), and its overexpression is associated with poorer prognosis.

Gene_expression (overexpressed) of EGFR associated with colon cancer and solid tumor

12) Confidence 0.56 Published 2010 Journal Current Oncology Section Abstract Doc Link PMC2901793 Disease Relevance 0.56 Pain Relevance 0

Because EGFR seemed to be expressed in all DRG-neurons (in contrast to the GDNF or NGF receptors described to be expressed only in a subset of cells [16,41]) we expected more EGF than NGF or GDNF responding cells.

Gene_expression (expressed) of EGFR in neurons

13) Confidence 0.41 Published 2010 Journal Mol Pain Section Body Doc Link PMC3023724 Disease Relevance 0 Pain Relevance 0

First we tested, if EGF can potentially act directly on the nociceptive neuron by checking for expression of the EGF receptor (EGFR) in DRGs.

Gene_expression (expression) of EGFR in neuron associated with nociception

14) Confidence 0.41 Published 2010 Journal Mol Pain Section Body Doc Link PMC3023724 Disease Relevance 0.19 Pain Relevance 0.10

Thus, we analyzed the expression of EGFR in DRG-sections and dissociated DRG-neuron cultures using immunofluorescence microscopy (Figure 3B, C).

Spec (analyzed) Gene_expression (expression) of EGFR in neuron

15) Confidence 0.41 Published 2010 Journal Mol Pain Section Body Doc Link PMC3023724 Disease Relevance 0.17 Pain Relevance 0.08

RT-PCR showed an amplification of an EGFR specific fragment at the expected size indicating that EGFR is expressed on the level of mRNA (Figure 3A) in rat DRG (rat brain serving as positive control [40]).

Gene_expression (expressed) of EGFR in brain

16) Confidence 0.41 Published 2010 Journal Mol Pain Section Body Doc Link PMC3023724 Disease Relevance 0.18 Pain Relevance 0.09

Indeed, while there is strong pressure to report cellular responses to EGF in EGFR expressing cells, also other studies show EGFR expression [59,60] in adult DRG but fail to detect EGF induced Erk1/2 signalling activity in cell culture.

Gene_expression (expression) of EGFR

17) Confidence 0.41 Published 2010 Journal Mol Pain Section Body Doc Link PMC3023724 Disease Relevance 0.13 Pain Relevance 0.05

EGFR is expressed in DRG-neurons

Gene_expression (expressed) of EGFR in neurons

18) Confidence 0.41 Published 2010 Journal Mol Pain Section Body Doc Link PMC3023724 Disease Relevance 0.14 Pain Relevance 0.08

This suggests that EGFR is expressed not just in a subpopulation but in all DRG-neurons (Figure 3D).

Neg (not) Gene_expression (expressed) of EGFR in neurons

19) Confidence 0.41 Published 2010 Journal Mol Pain Section Body Doc Link PMC3023724 Disease Relevance 0 Pain Relevance 0

In contrast to the growth factors NGF and GDNF, EGF failed to induce Erk1/2 phosphorylation even though the EGFR is expressed in all DRG-neurons and the STAT3 signalling pathway is initiated by EGF in DRG-neurons.

Gene_expression (expressed) of EGFR in neurons

20) Confidence 0.41 Published 2010 Journal Mol Pain Section Body Doc Link PMC3023724 Disease Relevance 0.09 Pain Relevance 0.03

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