In vitro studies of steroid receptors in NF1

NF1 类固醇受体的体外研究

• 批准号: 7115023
• 负责人: Lauren Michelle Fishbein
• 金额: $ 1.43万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-31 至 2006-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7115023
• 关键词: Schwann cells; androgen receptor; apoptosis; cell proliferation; estradiol; estrogen receptors; gene expression; hormone regulation /control mechanism; hormone therapy; immunocytochemistry; immunofluorescence technique; inhibitor /antagonist; ligands; neoplastic growth; nerve sheath neoplasm; neurofibroma; neurofibromatosis; polymerase chain reaction; progesterone receptors; protein localization; protein structure function; receptor expression; steroid hormone; steroid hormone receptor; terminal nick end labeling; tissue /cell culture; western blottings

Neurofibromatosis type I (NF1), a common dominant condition, is characterized by abnormal proliferation of neural crest derived cells, including Schwann cells (thought to be the clonal element) in neurofibromas. The current therapy for neurofibromas is surgery, which is usually insufficient. Neurofibromas are often aggravated during puberty and pregnancy, suggesting an altered sensitivity to steroid hormones. NF1 patients and their physicians worry about this possible correlation when faced with decisions about hormone therapies for birth control, menopause, or disease treatments. To investigate this hypothesis, the type, relative quantity and localization of hormone receptors present in NF1 tumor Schwann cell cultures compared to normal Schwann cells will be measured through RT-PCR/Western blot and immunofluorescence, respectively. To investigate the functional role of these receptors, the tumor cultures will be assayed for increased proliferation and/or survival in response to these hormones. Expression of genes believed to be downstream targets of steroid hormones will also be analyzed. These studies will characterize the role of hormones in neurofibroma development, allowing for more educated medical decisions, as well as identifying potential targets for inhibiting tumor development.

神经纤维瘤病I型（NF1）是一种常见的显性疾病，其特征是神经rest衍生的细胞的异常增殖，包括神经纤维纤维瘤中的Schwann细胞（被认为是克隆元素）。当前的神经纤维瘤疗法是手术，通常不足。神经纤维瘤通常在青春期和妊娠期间加重，表明对类固醇激素的敏感性改变了。 NF1患者及其医生会担心这种可能的相关性在面临有关生育，更年期或疾病治疗的激素疗法的决定时。为了研究这一假设，将分别通过RT-PCR/Western印迹和免疫荧光测量NF1肿瘤schwann细胞培养物中存在的激素受体的类型，相对数量和定位。为了研究这些受体的功能作用，将分析肿瘤培养物，以增加增殖和/或生存，以响应这些激素。也将分析认为是类固醇激素下游靶标的基因的表达。这些研究将表征激素在神经纤维瘤发育中的作用，从而做出更多受过教育的医疗决策，并确定抑制肿瘤发育的潜在靶标。