17beta-estradiol induces up-regulation of PTEN and PPARgamma in leiomyoma cells, but not in normal cells.
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.
Jeong
Young-Ju
YJ
Department of Obstetrics and Gynecology, Chonbuk National University Medical School, Jeonju 561-180, Korea.
Noh
Eun-Mi
EM
Lee
Young-Rae
YR
Yu
Hong-Nu
HN
Jang
Kyu-Yun
KY
Lee
Seung Jin
SJ
Kim
Jonghyeon
J
Kim
Jong-Suk
JS
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
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