Administration of βHCG leads to dose-dependent changes of gene expression signature of endometriotic stromal cells
Abstract
Preliminary studies have shown that systemic β-human chorionic gonadotrophin (βHCG) therapy alleviates endometriosis-related chronic pelvic pain. The underlying mechanism, however, is completely unknown. This study has investigated the dose-dependent alterations in the overall gene expression profile of endometriosis-derived stromal cells under increasing concentrations of βHCG by using the Affymetrix GeneChip U133 Set. It has been previously shown that βHCG concentrations of 0.1
U/ml and higher lead to a significant and dose-dependent increase in the expression of 68 genes. This study reports on a cluster analysis which identified three clusters of genes with a comparable expression pattern in response to increasing concentrations of βHCG. Most of the up-regulated genes encoded proteins that are involved in cell adhesion, intercellular communication, extracellular matrix remodelling, apoptosis and inflammation. Stromal monocultures from eight patients, treated with and without 50U/ml of βHCG, were then incubated and real-time polymerase chain reaction for the highly up-regulated genes PAI2, DUSP6, PLAU and MMP1 performed in order to validate the cDNA array findings in patients with endometriosis. Taken together, this study shows that βHCG induces dose-dependent characteristic response clusters in the gene expression profile of stromal cells obtained from endometriotic lesions which could explain the differential biological responses of βHCG in endometriosis.
Keywords: βHCG, cDNA array, endometriosis, gene expression signature
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Dr Singer is a board-certified gynaecologist and professor at the Medical University of Vienna. After graduation from Innsbruck University Medical School he successfully completed postdoctoral fellowships at Georgetown University (USA) and at the University of Leuven (Belgium), where he studied the influence of hormones on the development of malignant tumours. Professor Singer works and teaches at the Medical University of Vienna, where he has specialized in the treatment of breast cancer and the alleviation of climacteric symptoms. He was appointed Associated Professor of Obstetrics and Gynecology in 2004 and directs the clinic for hereditary breast and ovarian cancer at the Vienna General Hospital.
PII: S1472-6483(10)00046-5
doi:10.1016/j.rbmo.2010.01.010
© 2010 Published by Elsevier Inc.
