17 beta-estradiol induces up-regulation of PTEN and PPAR gamma in leiomyoma cells, but not in normal cells

Abstract

The tumor suppressor protein, PTEN (phosphatase and tensin homologue), has been reported to play a crucial role in a variety of tumor cells. Recent studies indicate that the transcription factor, PPAR gamma (peroxisome proliferator-activated receptor gamma) up-regulates PTEN expression transcriptionally through the binding of two response elements in the genomic sequence upstream of PTEN in tumor cells. Here, we determined the PTEN and PPAR gamma expression in human leiomyomas, and whether estrogen can change their protein expressions in cultured leiomyoma cells. Immunohistochemical staining and Western blot analysis revealed that PTEN protein levels in leiomyomas were higher than that the adjacent normal myometrial tissues, which was paralleled with decrease in phospho-Akt (ser-473) and phosphatidylinositol 3,4,5-tris phosphate (PIP(3)) level. Interestingly, leiomyomas exhibit high PPAR gamma expression compared to the adjacent normal myometrial tissues. In addition, we found that 17 beta-estradiol (E2) significantly stimulated PTEN and PPAR gamma expression in cultured leiomyoma cells, but did not change both protein levels in normal cells. This report shows the first evidence that PTEN and PPAR gamma are up-regulated in leiomyoma tissues, and estrogen stimulates expression of PTEN and PPAR gamma in leiomyoma cells, but not in normal cells.