PROSTATE CANCER & VITAMIN D--RECEPTORS, RESPONSES & RACE

前列腺癌

• 批准号: 2112564
• 负责人: GARY G SCHWARTZ
• 金额: $ 24.2万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-15 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2112564
• 关键词: African American; Hispanic Americans; RNA; bioassay; cancer risk; caucasian American; clone cells; genetic transcription; human subject; ligands; neoplasm /cancer invasiveness; northern blottings; prostate neoplasms; racial /ethnic difference; receptor; receptor binding; reporter genes; transfection; vitamin D

The Principal lnvestigator and colleagues have pioneered the hypothesis that deficiencies of 1,25-Dihydroxyvitamin D (1,25 D) increase the risk for clinical prostate cancer. This hypothesis led us to investigate the effects of vitamin D on established prostate cancer cell lines. We found that cells from an invasive prostate cancer cell line did not respond to vitamin D despite the presence of vitamin D receptors; whereas, a non- invasive prostate cancer cell line was sensitive to 1 ,25 D. This suggests that a deficient response to 1,25 D may be a characteristic of invasive prostate cancer cells. We will test the hypothesis that invasive prostate cancer cells exhibit diminished biochemical response to vitamin D compared to non-cancer prostate cells. Our Specific Aims are to: 1. ascertain vitamin D receptor levels and vitamin D responsiveness in invasive prostate cancer cells and in non-cancer prostate cells; 2. determine how these receptor levels and responses differ among men from 3 racial/ethnic groups at different risk for prostate cancer. In order to realize these aims we will: 1. Obtain surgical specimens of fresh prostatic tissue from Black, White, and Hispanic prostate cancer patients undergoing radical prostatectomy at the University of Miami/Jackson Memorial Medical Center; 2. Prepare primary cultures of invasive prostate cancer and non-cancer prostate cells from each patient using an in vitro cell invasion assay; 3. Assess vitamin D receptor levels and vitamin D receptor function by reporter gene assay. Our primary goal is to determine whether vitamin D sensitivity differentiates invasive prostate cancer from non-cancerous prostate cells. This research may ultimately permit the identification of those prostate cancers that are likely to be invasive. The identification of invasive prostate cancer is critical in determining which men should receive aggressive treatment for their disease.

首席调查员和他的同事们率先提出了一个假设 缺乏1，25-二羟基维生素D（1，25 D）会增加 临床前列腺癌的治疗。这一假设促使我们调查了 维生素D对已建立的前列腺癌细胞系的影响。我们发现 来自侵袭性前列腺癌细胞系的细胞对 维生素D受体的存在;然而，非- 侵袭性前列腺癌细胞系对1，25 D敏感。这 表明对1，25 D的反应不足可能是 侵袭性前列腺癌细胞。我们将检验侵入性的假设 前列腺癌细胞对维生素C的生物化学反应减弱 与非癌前列腺细胞相比。我们的具体目标是：1。 确定维生素D受体水平和维生素D反应性， 侵袭性前列腺癌细胞和非癌前列腺细胞; 2. 确定这些受体水平和反应在男性中的差异， 3个不同种族/民族的前列腺癌风险。 为了实现这些目标，我们将：1。获取以下的手术标本 来自黑人、白色和西班牙裔前列腺癌的新鲜前列腺组织 接受根治性乳房切除术的患者， 迈阿密/杰克逊纪念医疗中心; 2.制备以下的原代培养物 来自每个患者的侵袭性前列腺癌和非癌前列腺细胞 使用体外细胞侵袭测定; 3.评估维生素D受体 水平和维生素D受体功能的报告基因测定。我们 主要目标是确定维生素D敏感性是否与 非癌性前列腺细胞的侵袭性前列腺癌。本研究 可能最终允许识别那些前列腺癌， 很可能是侵入性的。浸润性前列腺癌的鉴别 是决定哪些男性应该接受积极治疗的关键 因为他们的疾病。