title: Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore MD 21224, USA. h-honda@qg8.so-net.ne.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Honda
authors.forename: Fermin F
authors.initials: FF
authors.lastname: Barrueto
authors.forename: Jean
authors.initials: J
authors.lastname: Gogusev
authors.forename: Dwight D
authors.initials: DD
authors.lastname: Im
authors.forename: Patrice J
authors.initials: PJ
authors.lastname: Morin
mesh_terms: D004715:Endometriosis / Q000209:etiology / Q000503:physiopathology*; D004717:Endometrium / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D015513:Oncogene Proteins / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D055765:Shc Signaling Adaptor Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D015854:Up-Regulation; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human