Steroid hormonal regulation of proliferative, p53 tumor suppressor, and apoptotic responses of sheep ovarian surface epithelial cells
Steroid hormonal regulation of proliferative, p53 tumor suppressor, and apoptotic responses of sheep ovarian surface epithelial cells
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DOI：
10.1016/s0303-7207(01)00675-x
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发表时间：
2002-01-15
影响因子：
4.1
通讯作者：
Van Kirk, EA
中科院分区：
文献类型：
--
作者：
Murdoch, WJ;Van Kirk, EA
卵巢表面上皮细胞参与了常见卵巢癌的发生。卵巢表面与排卵期柱头相邻的上皮细胞DNA完整性在破裂过程中受到损害；大多数细胞因凋亡而退化，但也有一些带有亚致死性病变的细胞沿卵泡边缘持续存在。基因损伤的表面上皮细胞（即DNA未修复，但未死亡）的克隆扩增可能导致卵巢癌。假设雌二醇和黄体酮调节卵巢表面上皮细胞周期动力学，与卵泡-黄体过渡和排卵伤口修复/重塑相关，孕酮上调肿瘤抑制因子p53，抑制基线和雌二醇刺激的体外培养绵羊卵巢表面上皮细胞增殖。对类固醇激素的抗/有丝分裂反应是转录和受体依赖的。细胞凋亡率（DNA断裂）不受黄体酮影响。高浓度雌二醇通过非基因组（可能是抗氧化）机制抑制基础和h2o2诱导的细胞凋亡。我们建议，黄体激素在整个黄体期抑制卵巢表面上皮细胞的增殖，为纠正排卵过程中不可避免的副产品DNA代谢紊乱提供了必要的时间（生长停滞）。随着黄体溶解和雌激素促排卵前卵泡的优势，卵巢表面上皮随后再生。因此，可以想象，卵巢周期的类固醇激素环境的扰动可能是卵巢表面上皮细胞癌变的易感因素。(C) 2002爱思唯尔科学爱尔兰有限公司版权所有。
Ovarian surface epithelial cells have been implicated in the genesis of common ovarian cancers. The integrity of DNA of ovarian surface epithelial cells contiguous with the ovulatory stigma becomes compromised during the rupture process; most cells degenerate by apoptosis, however some, bearing sublethal lesions, persist along the margins of ovulated follicles. Clonal expansion of a genetically-damaged surface epithelial cell (i.e. with unrepaired DNA, but not committed to death) can presumably give rise to ovarian carcinoma. It was hypothesized that estradiol and progesterone regulate ovarian surface epithelial cell-cycle dynamics associated with folliculo-luteal transitions and ovulatory wound repair/remodeling, Progesterone up-regulated the tumor suppressor p53 and inhibited baseline and estradiol-stimulated proliferation of cultured sheep ovarian surface epithelial cells. Anti/mitotic responses to steroid hormones were transcriptionally- and receptor- dependent. Rates of apoptosis (DNA fragmentation) were unaffected by progesterone. High concentrations of estradiol, via a nongenomic (perhaps antioxidant) mechanism, suppressed basal and H2O2-induced apoptosis. We suggest that, progesterone serves to inhibit proliferation of ovarian surface epithelial cells throughout the luteal phase-providing the time (growth arrest) required to correct any metabolic disturbances to DNA that are perpetrated as an inevitable by-product of the ovulatory process. With luteolysis and dominance of an estrogenic preovulatory follicle the ovarian surface epithelium is then regenerated. Thus, it is conceivable that perturbations to the steroid hormonal milieu of ovarian cycles could be a predisposing factor for cancerous transformation of an ovarian surface epithelial cell. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.