Administration of betaHCG leads to dose-dependent changes of gene expression signature of endometriotic stromal cells.
Preliminary studies have shown that systemic beta-human chorionic gonadotrophin (betaHCG) 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 betaHCG by using the Affymetrix GeneChip U133 Set. It has been previously shown that betaHCG concentrations of 0.1U/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 betaHCG. 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 betaHCG, 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 betaHCG 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 betaHCG in endometriosis.
Hudelist
Gernot
G
Division of Special Gynecology, Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.
Huber
Ambros
A
Auer
Michael
M
Knöfler
Martin
M
Saleh
Leila
L
Hrachowitz
Christian
C
Huber
Johannes C
JC
Kubista
Ernst
E
Manavi
Mahmood
M
Bilban
Martin
M
Singer
Christian F
CF
D000328:Adult; D019002:CD56 Antigen / Q000378:metabolism; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D019002:CD56 Antigen; D018997:Chorionic Gonadotropin, beta Subunit, Human; D014746:Vimentin; D017493:Leukocyte Common Antigens