Kovács Kálmán A, Lengyel Ferenc, Vértes Zsuzsanna, Környei József L, Gocze Péter M, Sumegi Balazs, Szabó István, Vértes Marietta
Department of Obstetrics and Gynecology, Pécs University Medical School, Edesanyák u 13/15, Pécs H-7624, Hungary.
J Steroid Biochem Mol Biol. 2007 Feb;103(2):196-9. doi: 10.1016/j.jsbmb.2006.08.006. Epub 2006 Nov 9.
PTEN phosphatase, a product of PTEN tumor suppressor gene, exists in cells in phosphorylated and unphosphorylated form and has a central role in regulation of PI3K/Akt signalling which is involved in non-genomic action of estradiol. The purpose of this study was to analyze the level of total PTEN and phosphoPTEN parallel to phosphoAkt in leiomyoma and adjacent myometrium during menstrual cycle and at menopause. The expression of total PTEN in leiomyoma and myometrium did not change throughout the experiments. However, the level of phosphoPTEN was increased in leiomyoma during menstrual cycle. The phosphorylation of PTEN in myometrium was lower during secretory phase than that of proliferative phase. The phosphoAkt was abundant in leiomyoma, and its expression was higher during menstrual cycle than in myometrium. The phosphorylation of PTEN was directly related to phosphoAkt, suggesting a direct link between the inactivation of PTEN and activation of Akt. At the decline of sexual steroids, at menopause, no differences were observed in the expression of studied proteins between the two types of tissues. Our results suggest that the altered phosphorylation of PTEN protein and the consequent activation of survival signals may contribute to the pathomechanism of leiomyoma.
PTEN磷酸酶是PTEN肿瘤抑制基因的产物，以磷酸化和非磷酸化形式存在于细胞中，在调节PI3K/Akt信号传导中起核心作用，而该信号传导参与雌二醇的非基因组作用。本研究的目的是分析月经周期和绝经期间平滑肌瘤及邻近子宫肌层中总PTEN、磷酸化PTEN与磷酸化Akt水平的平行关系。在整个实验过程中，平滑肌瘤和子宫肌层中总PTEN的表达没有变化。然而，月经周期中平滑肌瘤中磷酸化PTEN的水平升高。子宫肌层中PTEN的磷酸化在分泌期低于增殖期。磷酸化Akt在平滑肌瘤中含量丰富，其表达在月经周期中高于子宫肌层。PTEN的磷酸化与磷酸化Akt直接相关，提示PTEN失活与Akt激活之间存在直接联系。在性类固醇水平下降的绝经时，两种组织中所研究蛋白质的表达未观察到差异。我们的结果表明，PTEN蛋白磷酸化改变及随之而来的生存信号激活可能促成平滑肌瘤的发病机制。
