Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis

Hiroshi Honda, Fermin Barrueto, Fermin F Barrueto, Jean Gogusev, Dwight D Im, Patrice J Morin
Reproductive biology and endocrinology : RB&E · 2008 · vol. 6(1) , pp. 59 · doi:10.1186/1477-7827-6-59 · PMID:19055724 · W2141369228
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Serial analysis of gene expression identified upregulated genes AXL and SHC1 in endometriosis, suggesting PI3K-Akt and MAPK pathway activation involved in disease pathogenesis.

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Abstract

BACKGROUND: Endometriosis is a clinical condition that affects up to 10% of the women of reproductive age. Endometriosis is characterized by the presence of endometrial tissues outside the uterine cavity and can lead to chronic pelvic pain, infertility and, in some cases, to ovarian cancer. METHODS: In order to better understand the pathogenesis of endometriosis, we have used Serial Analysis of Gene Expression (SAGE) to identify genes differentially in this disease by studying three endometriotic tissues and a normal endometrium sample. Promising candidates (AXL, SHC1, ACTN4, PI3KCA, p-AKT, p-mTOR, and p-ERK) were independently validated by immunohistochemistry in additional normal and endometriotic tissues. RESULTS: We identified several genes differentially expressed between endometriosis and normal endometrium. IGF2, ACTN4, AXL, and SHC1 were among the most upregulated genes. Comparison of the endometriosis gene expression profiles with the gene expression patterns observed in normal human tissues allowed the identification of endometriosis-specific genes, which included several members of the MMP family (MMP1,2,3,10,11,14). Immunohistochemical analysis of several candidates confirmed the SAGE findings, and suggested the involvement of the PI3K-Akt and MAPK signaling pathways in endometriosis. CONCLUSION: In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. These genes, as well as others identified as differentially expressed in this study, may be useful for the development of novel strategies for the detection and/or therapy of endometriosis.

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Condition tags

endometriosischronic_pelvic_paininfertility

MeSH descriptors

Endometriosis Endometrium Oncogene Proteins Receptor Protein-Tyrosine Kinases Shc Signaling Adaptor Proteins Axl Receptor Tyrosine Kinase Endometriosis Endometriosis Endometrium Extracellular Signal-Regulated MAP Kinases Extracellular Signal-Regulated MAP Kinases Female Gene Expression Profiling Gene Expression Regulation Humans Oncogene Proteins Phosphatidylinositol 3-Kinases Phosphatidylinositol 3-Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt

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