Research

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 Honda¹ , Fermin F Barrueto² , Jean Gogusev³ , Dwight D Im² and Patrice J Morin^1,4

¹  Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore MD 21224, USA

²  The Gynecology Center, Mercy Hospital, Baltimore, MD 21202, USA

³  INSERM U507, Hôpital Necker, Paris, France

⁴  Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA

author email corresponding author email

Reproductive Biology and Endocrinology 2008, 6:59doi:10.1186/1477-7827-6-59

Published:	2 December 2008

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.