INT205081

Context Info Confidence 0.58 First Reported 2007 Last Reported 2008 Negated 0 Speculated 1 Reported most in Body Documents 10 Total Number 11 Disease Relevance 11.27 Pain Relevance 2.37

cell differentiation (AXL) signal transduction (AXL) plasma membrane (AXL)

Anatomy Link Frequency thyroid 2 endometrium 2 AXL (Homo sapiens)

Pain Link Frequency Relevance Heat endometriosis 864 99.16 Somatostatin 2 56.96 pain pelvic 16 52.92 addiction 4 48.32 metalloproteinase 6 11.36 cytokine 9 5.00 Inflammation 8 5.00 Dismenorea 8 5.00 Thalamus 8 5.00 Chronic pancreatitis 2 5.00

Disease Link Frequency Relevance Heat Islet Cell Adenoma 58 99.84 Leukemia 6 99.84 Skin Cancer 4 99.44 Endometriosis 1104 99.16 Hypoxia 7 99.12 Fibrosarcoma 2 98.88 Cancer 207 98.82 Renal Cancer 55 97.74 Thyroid Neoplasm 2 97.68 Ovarian Cancer 121 97.16

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Co-overexpression of AXL with Gas6 has also been reported in several types of tumors including ovarian cancer [45], and may therefore have an important role in uncontrolled cell growth/proliferation.

Positive_regulation (overexpression) of Gene_expression (overexpression) of AXL associated with cancer and ovarian cancer

1) Confidence 0.58 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2615013 Disease Relevance 0.91 Pain Relevance 0.28

AXL expression is also elevated in leukemia, melanoma, prostate, colon, endometrial, and thyroid cancers[29]–[32].

Positive_regulation (elevated) of Gene_expression (expression) of AXL in thyroid associated with thyroid neoplasm, leukemia and skin cancer

2) Confidence 0.56 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1824711 Disease Relevance 1.15 Pain Relevance 0.03

Although, the comparison of gene expression profiles between endometriosis and normal endometrium was done for the proliferative phase, AXL, SHC1, and ACTN4 (discussed below) were also overexpressed during secretory phase in ovarian endometriosis.

Positive_regulation (overexpressed) of Gene_expression (overexpressed) of AXL in endometrium associated with endometriosis

3) Confidence 0.51 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2615013 Disease Relevance 1.18 Pain Relevance 0.42

Therefore, it is possible that overexpression of AXL and GAS6 is a main cause for the activation of the PI3K-Akt pathway in endometriosis.

Spec (possible) Positive_regulation (overexpression) of Gene_expression (overexpression) of AXL associated with endometriosis

4) Confidence 0.42 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2615013 Disease Relevance 0.79 Pain Relevance 0.24

Overexpression of both AXL and GAS6 in ovarian endometriosis has previously been demonstrated using RT-PCR analysis and IHC [44].

Positive_regulation (Overexpression) of Gene_expression (Overexpression) of AXL associated with endometriosis

5) Confidence 0.42 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2615013 Disease Relevance 0.91 Pain Relevance 0.27

Similar to what we observed for AXL, SHC1 was found consistently elevated in the studied endometriotic samples.

Positive_regulation (observed) of Gene_expression (observed) of AXL associated with endometriosis

6) Confidence 0.42 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2615013 Disease Relevance 0.78 Pain Relevance 0.19

Therefore, it is possible that overexpression of AXL and GAS6 is a main cause for the activation of the PI3K-Akt pathway in endometriosis.

Positive_regulation (cause) of Gene_expression (overexpression) of AXL associated with endometriosis

7) Confidence 0.42 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2615013 Disease Relevance 0.79 Pain Relevance 0.24

As overexpression of AXL and SHC1 theoretically activates both PI3K-Akt and MAPK pathways, dysregulation of these genes in human endometriosis may correspond to oncogenic activation of K-ras or biallelic losses of Pten in the mouse model of the disease.

Positive_regulation (overexpression) of Gene_expression (overexpression) of AXL associated with endometriosis and disease

8) Confidence 0.39 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2615013 Disease Relevance 1.10 Pain Relevance 0.38

In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively.

Positive_regulation (overexpression) of Gene_expression (overexpression) of AXL associated with endometriosis

9) Confidence 0.39 Published 2008 Journal Reprod Biol Endocrinol Section Abstract Doc Link PMC2615013 Disease Relevance 0.93 Pain Relevance 0.34

Our analysis identified additional genes, including AXL, MFAB, and AXIN2, whose elevated expression in islet cell tumors suggests signal transduction pathways important in their development.

Positive_regulation (elevated) of Gene_expression (expression) of AXL associated with islet cell adenoma

10) Confidence 0.33 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1824711 Disease Relevance 1.59 Pain Relevance 0

They include carbonic anyhdrase IX, which is the RCC associated antigen G250 and is induced in many cancer types, hypoxia induced gene ADORA3, potentially oncogenic AXL gene which causes transformation when overexpressed in NIH 3T3 cells, and vitamin D receptor (VDR, up-regulated), which was found to be over-expressed in pancreatic cell lines (Albrechtsson et al. 2003) and is down-regulated by resveratrol compound (Shi et al. 2004) in RCC cell lines, which acts as a chemopreventive agent for RCC and other types of cancers.

Positive_regulation (overexpressed) of Gene_expression (overexpressed) of AXL gene associated with hypoxia, cancer and renal cancer

11) Confidence 0.26 Published 2007 Journal Cancer Informatics Section Body Doc Link PMC2675843 Disease Relevance 1.14 Pain Relevance 0

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