RETINOIC ACID RECEPTORS IN ESTROGENIZED RAT PROSTATE

雌激素化大鼠前列腺中的视黄酸受体

• 批准号: 2905179
• 负责人: WILLIAM Y CHANG
• 金额: $ 4.33万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2905179
• 关键词: cell differentiation; estrogens; high performance liquid chromatography; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; laboratory rat; newborn animals; northern blottings; polymerase chain reaction; prostate; protein isoforms; receptor expression; reproductive development; retinoate; retinoid binding proteins; western blottings

prostate cancer is a leading cause of cancer deaths in men and still eludes medical treatment and prevention. It has been speculated that this is due to the lack of comprehensive understanding about the processes of normal development and growth of the prostate. Aberrations in growth and development are thought to be critical processes which lead to cancerous growths. Vitamin A is a key regulator of normal organ development and the major active form of vitamin A in this process is a derivative called retinoic acid. We propose that a reduction in retinoic acid efficacy may lead to abnormal development of the prostate. To test this theory, we will use the neonatally estrogenized rat prostate , a model which exhibits stromal hyperplasia, reduced ductal morphogenesis, and retarded epithelial differentiation during neonatal development. These developmental aberrations imprint upon subsequent prostate growth such that the adult estrogenized prostate forms preneoplastic lesions (dysplasisas and adenomas). We will evaluate whether the function of retinoic acid in this animal model is deficient by evaluating the levels of retinoic acid and its receptor in the prostate. To validate our theory, we will supplement retinoic acid to the neonatally estrogenized rats to demonstrate whether retinoic acid can prevent developmental aberrations associated with estrogen treatment. If retinoic acid prevents the development of preneoplastic lesions, then it may warrant future human studies to evaluate its role in the prevention of prostate cancer.

前列腺癌是男性癌症死亡的主要原因， 逃避医学治疗和预防。 据推测 这是由于缺乏全面的了解， 前列腺的正常发育和生长过程。 生长和发育的异常被认为是至关重要的 导致癌症生长的过程。 维生素A是关键 正常器官发育的调节剂和主要活性形式 维生素A在这个过程中是一种叫做视黄酸的衍生物。 我们 提出维甲酸功效的降低可能导致 前列腺发育异常。 为了验证这一理论，我们将 使用卵巢雌激素化的大鼠前列腺，该模型表现出 间质增生，导管形态发生减少， 新生儿发育过程中的上皮分化。这些 发育异常对随后的前列腺生长的影响 使得成年雌激素化前列腺形成癌前病变 （发育不良和腺瘤）。 我们将评估 通过评估该动物模型中的视黄酸缺乏， 前列腺中视黄酸及其受体的水平。 到 验证我们的理论，我们将补充维甲酸到 通过对大鼠进行卵巢雌激素化来证明维甲酸是否可以 预防与雌激素治疗相关的发育异常。 如果维甲酸能阻止癌前病变的发展， 那么它可能会保证未来的人类研究，以评估其在 前列腺癌的预防