Mutter G L, Lin M C, Fitzgerald J T, Kum J B, Eng C
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
J Clin Endocrinol Metab. 2000 Jun;85(6):2334-8. doi: 10.1210/jcem.85.6.6652.
Frequent mutation of the PTEN tumor suppressor gene in endometrial adenocarcinoma has led to the prediction that its product, a phosphatase that regulates the cell cycle, apoptosis, and possibly cell adhesion, is functionally active within normal endometrial tissues. We examined PTEN expression in normal human endometrium during response to changing physiological levels of steroid hormones. PTEN ribonucleic acid levels, assessed by RT-PCR, increase severalfold in secretory compared to proliferative endometrium. This suggested that progesterone, a known antineoplastic factor for endometrial adenocarcinoma, increases PTEN levels. Immunohistochemistry with an anti-PTEN monoclonal antibody displayed a complex pattern of coordinate stromal and epithelial expression. Early in the menstrual cycle under the dominant influence of estrogens, the proliferative endometrium shows ubiquitous cytoplasmic and nuclear PTEN expression. After 3-4 days of progesterone exposure, glandular epithelium of early secretory endometrium maintains cytoplasmic PTEN protein in an apical distribution offset by expanding PTEN-free basal secretory vacuoles. By the midsecretory phase, epithelial PTEN is exhausted, but increases dramatically in the cytoplasm of stromal cells undergoing decidual change. We conclude that stromal and epithelial compartments contribute to the hormone-driven changes in endometrial PTEN expression and infer that abnormal hormonal conditions may, in turn, disrupt normal patterns of PTEN expression in this tissue.
子宫内膜腺癌中PTEN肿瘤抑制基因的频繁突变提示，其产物（一种调节细胞周期、细胞凋亡以及可能的细胞黏附的磷酸酶）在正常子宫内膜组织中具有功能活性。我们检测了正常人类子宫内膜在对甾体激素生理水平变化作出反应期间的PTEN表达情况。通过逆转录聚合酶链反应（RT-PCR）评估，与增殖期子宫内膜相比，分泌期子宫内膜的PTEN核糖核酸水平增加了数倍。这表明，已知的子宫内膜腺癌抗肿瘤因子孕酮可增加PTEN水平。使用抗PTEN单克隆抗体进行免疫组织化学检测显示，基质和上皮表达呈现出复杂的协同模式。在月经周期早期，在雌激素的主要影响下，增殖期子宫内膜显示出普遍存在的细胞质和细胞核PTEN表达。在孕酮作用3 - 4天后，早期分泌期子宫内膜的腺上皮细胞在顶端分布维持细胞质PTEN蛋白，但被不断扩大的无PTEN的基底分泌泡抵消。到分泌中期，上皮PTEN耗尽，但在发生蜕膜变化的基质细胞细胞质中显著增加。我们得出结论，基质和上皮部分共同促成了激素驱动的子宫内膜PTEN表达变化，并推断异常激素状况可能反过来破坏该组织中PTEN的正常表达模式。
