Identification of Genes Regulated by the Antiprogestin, Onapristone, in Breast Cancer Cells using Microarray Analysis.

Progesterone receptor (PR) antagonists are a potential new therapeutic strategy for the treatment of patients with invasive breast cancer (BC). One such progesterone antagonist is Onapristone. Onapristone has been reported to have strong anti-progestational and anti-tumor activity. A tumor remission rate of approximately 66% was found in a phase II clinical trial of Onapristone as a first-line endocrine therapy in post-menopausal patients with primary BC. However, during this trial, a minority of the patients developed abnormal liver function test results. As a consequence, the further therapeutic use off this drug has stop. Although the mechanism of action of Onapristone has been suggested by animal model experiments, the genes regulated by the drug in the breast are not known. In the present study, the BC cell line T47D was treated with Onapristone and examined with Affymetrix microarrays and real-time RT-PCR to identify genes which were differentially expressed. Cells were treated with Onapristone either alone or in the presence of progesterone, and microarray analysis carried out upon the RNA extracted from the cells. The expression of a selection of up- or down-regulated genes observed was further investigated using real-time RT-PCR. In addition, the expression of these genes was investigated in the PR− cell line, MDA-MB-231 treated with Onapristone, to ensure that any changes in gene expression observed, were due to Onapristone effects via the PR. [ABSTRACT FROM AUTHOR]