title: 17beta-estradiol induces up-regulation of PTEN and PPARgamma 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, PPARgamma (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 PPARgamma 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 (PIP3) level. Interestingly, leiomyomas exhibit high PPARgamma expression compared to the adjacent normal myometrial tissues. In addition, we found that 17beta-estradiol (E2) significantly stimulated PTEN and PPARgamma expression in cultured leiomyoma cells, but did not change both protein levels in normal cells. This report shows the first evidence that PTEN and PPARgamma are up-regulated in leiomyoma tissues, and estrogen stimulates expression of PTEN and PPARgamma in leiomyoma cells, but not in normal cells.
authors.affiliation: Department of Obstetrics and Gynecology, Chonbuk National University Medical School, Jeonju 561-180, Korea.
authors.forename: Young-Ju
authors.initials: YJ
authors.lastname: Jeong
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Noh
authors.forename: Young-Rae
authors.initials: YR
authors.lastname: Lee
authors.forename: Hong-Nu
authors.initials: HN
authors.lastname: Yu
authors.forename: Kyu-Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Jonghyeon
authors.initials: J
authors.lastname: Kim
authors.forename: Jong-Suk
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000328:Adult; D015153:Blotting, Western; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009215:Myometrium / Q000201:enzymology* / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014594:Uterine Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: D047495:PPAR gamma; D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate; D004958:Estradiol; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human