Role of Estrogen in Cervical Cancer

雌激素在宫颈癌中的作用

• 批准号: 7534381
• 负责人: PAUL F. LAMBERT
• 金额: $ 27.64万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7534381
• 关键词: Applications Grants; Carcinogens; Cause of Death; Cervical; Estrogen Receptors; Estrogens; Exposure to; Genome; Growth; HPV-High Risk; Human; Human Papillomavirus; Maintenance; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Mediating; Oncogenes; Pharmaceutical Preparations; Property; Role; Transgenic Mice; Viral Genes; Viral Oncogene; Woman; Xenograft Model; carcinogenesis; cell type; cofactor; mouse model; pre-clinical; preclinical study; prevent; receptor; reproductive hormone; research study; tumorigenic

Human cervical cancer is a leading cause of death by cancer among women worldwide. It is caused by a subset of anogenital Human papillomaviruses (HPVs). The genomes of these high risk HPVs are found present in virtually all human cervical cancers and a subset of viral genes, E6 and E7 commonly expressed. E6 and E7 possess transforming and tumorigenic properties leading to their definition as oncogenes. Cervical cancer arises over a period of decades following initial exposure to these high risk HPVs, and a number of cofactors have been identified including reproductive hormones. In a prior study using a transgenic mouse model for HPV-associated cervical cancer we determined that, in addition to these two viral oncogenes, estrogen contributes not only to the genesis of cervical cancer but also its maintenance and continued growth. In this grant application we propose experiments to evaluate the role of estrogen receptor (ER)-dependent versus ER-independent mechanisms of estrogen-mediated carcinogenesis in this mouse model for human cervical cancer. We also propose experiments to assess the efficacy of anti-estrogenic drugs in preventing and treating cervical cancer. These preclinical studies should determine whether estrogen and its receptors are valid targets in preventing and treating human cervical cancer.

人类宫颈癌是全世界女性癌症死亡的主要原因。它是造成的 由肛门生物乳头瘤病毒（HPV）的子集。这些高风险HPV的基因组是 在几乎所有人类的宫颈癌中存在的存在和病毒基因的子集E6和E7的子集 表达。 E6和E7具有转化和肿瘤特性，导致其定义为 癌基因。宫颈癌在初次接触这些高的几十年中出现了 风险HPV和许多辅助因子已被确定，包括生殖激素。在先前 使用转基因小鼠模型进行HPV相关的宫颈癌的研究，我们确定 除了这两种病毒癌基因，雌激素不仅促进了宫颈癌的起源 而且它的维护和持续增长。在此赠款申请中，我们建议实验 评估雌激素受体（ER）依赖性与与ER独立的机制的作用 雌激素介导的人类宫颈癌的小鼠模型中的癌变。我们也建议 评估抗雌激素在预防和治疗宫颈癌方面的疗效的实验。 这些临床前研究应确定雌激素及其受体是否是有效的靶标 预防和治疗人宫颈癌。