Progesterone receptor modulator CDB-2914 induces extracellular matrix metalloproteinase inducer in cultured human uterine leiomyoma cells
Xu,Qin; Ohara,Noriyuki; Liu,Jin; Amano,Mariko; Sitruk-Ware,Regine; Yoshida,Shigeki; Maruo,Takeshi
Molecular Human Reproduction 14(3): 181-191
Publication date: 2008
Effects of progesterone receptor modulator CDB-2914 on the expressionof the extracellular matrix (ECM) components were examined incultured human uterine leiomyoma and myometrial cells. ECM metalloproteinaseinducer (EMMPRIN), matrix metalloproteinases (MMPs), tissueinhibitors of MMP (TIMPs) and collagen levels were assessedby Western blot analysis, MMP activity assay and real-time RT-PCR.RNA interference (RNAi) of EMMPRIN was performed using smallinterfering mRNA. In cultured leiomyoma cells, CDB-2914 treatmentat concentrations greater than or equal to 10 M significantlyincreased EMMPRIN, MMP-1 and MMP-8 protein contents and MMP-1,MMP-2, MMP-3 and MMP-9 mRNA levels, and activity of MMP-1, MMP-2,MMP-3 and MMP-9 in the medium. TIMP-1 and TIMP-2 were significantlydecreased at mRNA and protein levels by CDB-2914 treatment atconcentrations 10 M in these cells. CDB-2914 treatmentdecreased types I and III collagen protein contents. However,CDB-2914 treatment did not affect the ECM component expressionin cultured myometrial cells. RNAi of EMMPRIN abrogated CDB-2914-mediatedboth induction of MMPs and reduction of TIMPs and collagensin cultured leiomyoma cells. These results suggest that CDB-2914modulates the expression of EMMPRIN, MMPs, TIMPs and collagensin cultured leiomyoma cells without comparable effects on myometrialcells.