Administration of beta HCG leads to dose-dependent changes of gene expression signature of endometriotic stromal cells

作者:Hudelist Gernot; Huber Ambros; Auer Michael; Knoefler Martin; Saleh Leila; Hrachowitz Christian; Huber Johannes C; Kubista Ernst; Manavi Mahmood; Bilban Martin; Singer Christian F*
来源:Reproductive BioMedicine Online, 2010, 20(5): 699-706.
DOI:10.1016/j.rbmo.2010.01.010

摘要

Preliminary studies have shown that systemic beta-human chorionic gonadotrophin (beta HCG) 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 beta HCG by using the Affymetrix Gene Chip U133 Set. It has been previously shown that beta HCG 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 beta HCG. 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 50 U/ml of beta HCG, 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 beta HCG 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 beta HCG in endometriosis.

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