Reactive Oxygen Species in the Initiation, Survival and Racial Disparity of Uterine Leiomyoma

到目前为止，我们还不明白为什么绝经前子宫肌瘤的发病率如此之高。 我们也不了解在这种疾病中观察到种族差异的原因。黑人女性倾向于 至 组。 涉及到 角色 脱氧核糖核酸 假设 此外， 动态平衡 和 分析 单元格 将要 与其他种族相比，肿瘤发生得更早，数量更多，体积更大，症状更多 我们已经研究了与子宫肌瘤生长和生存有关的分子机制 对激素和信号转导途径的研究发现，活性氧(ROS)起着显著的作用 在肌瘤发病机制中的作用。此外，我们第一次发现，ROS水平和对 与白人妇女相比，黑人妇女子宫肌层和子宫肌瘤组织中的蛋白增加。我们 ROS促进MED12基因的突变，从而促进肌瘤的形成。在……里面 ROS促进子宫肌瘤的生长和存活，因为雌激素和孕激素提供了 保护肿瘤免受高ROS水平的毒性的环境。我们提出机械论 分子分析来验证我们的假设，包括对ROS慢性治疗的突变分析， ER和PR在染色质上的占有率对ROS的响应，我们测试了BCL2抑制剂的靶向性 当缺乏雌激素和黄体酮时，ROS会促进衰老。在我们所有的研究中，我们 比较黑人和白人女性的组织将产生有价值的和新的洞察力 在肌瘤中观察到的种族差异。我们将学习可能导致子宫肌瘤的早期变化 并为bcl2抑制剂治疗子宫肌瘤提供生物学基础。

To date, we do not understand why there is such a high prevalence of uterine leiomyoma in premenopausal women nor do we understand the reasons for the racial disparity observed in this disease. Black women tend to groups. pertains role DNA hypothesize addition, homeostatic and analysis cells will develop tumors earlier and are more numerous, larger in size and more symptomatic than other ethnic We have studied the molecular mechanisms involved in leiomyoma tumor growth and survival as it to hormones and signaling pathways and found that reactive oxygen species (ROS) plays a significant in leiomyoma pathogenesis. Moreover, for the first time, we discovered that ROS levels and effects on are increased in the myometrial and leiomyoma tissues of Black compared to White women. We that ROS promotes mutations in the MED12 gene, to promote leiomyoma tumor formation. In ROS promotes growth and survival of the leiomyoma tumors as estrogen and progesterone provide a environment to protect the tumors from the toxicity of high ROS levels. We propose mechanistic molecular analyses to test our hypothesis including mutational analysis upon chronic treatment with ROS, of ER and PR occupancy on chromatin in response to ROS, and we test the BCL2 inhibitors to target where ROS promotes senescence when estrogen and progesterone are absent. In all of our studies, we compare the tissues from Black versus white women which willgenerate valuable and novel insight into the racial disparity observed in leiomyoma. We will learn about early changes that may lead to leiomyoma development as well as provide biological rationale to treat leiomyoma tumors with the BCL2 inhibitors.