Department of Obstetrics and Gynecology, Chonbuk National University Medical School, Jeonju 561-180, Korea.
Int J Oncol. 2010 Apr;36(4):921-7. doi: 10.3892/ijo_00000571.
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.
抑癌蛋白 PTEN（磷酸酶和张力蛋白同源物）已被报道在多种肿瘤细胞中发挥关键作用。最近的研究表明，转录因子 PPARγ（过氧化物酶体增殖物激活受体 γ）通过结合肿瘤细胞中 PTEN 基因组序列上游的两个反应元件，在转录水平上上调 PTEN 的表达。在这里，我们测定了人子宫肌瘤中的 PTEN 和 PPARγ 表达，以及雌激素是否可以改变培养的子宫肌瘤细胞中它们的蛋白表达。免疫组织化学染色和 Western blot 分析显示，子宫肌瘤中的 PTEN 蛋白水平高于相邻的正常子宫肌层组织，这与磷酸化 Akt（ser-473）和磷脂酰肌醇 3,4,5-三磷酸（PIP3）水平的降低相平行。有趣的是，子宫肌瘤与相邻的正常子宫肌层组织相比，PPARγ 表达较高。此外，我们发现 17β-雌二醇（E2）可显著刺激培养的子宫肌瘤细胞中 PTEN 和 PPARγ 的表达，但对正常细胞中的两种蛋白水平没有影响。本报告首次表明，PTEN 和 PPARγ 在子宫肌瘤组织中上调，雌激素刺激子宫肌瘤细胞中 PTEN 和 PPARγ 的表达，但不刺激正常细胞中的表达。
