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

首席调查员及其同事率先提出了这一假说 缺乏1，25-二羟基维生素D(1，25D)会增加患病风险 用于临床前列腺癌。这一假说使我们研究了 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 尽管存在维生素D受体，但非维生素D 侵袭性前列腺癌细胞系对1，25D敏感。 提示对1，25-D的反应不足可能是 侵袭性前列腺癌细胞。我们将检验一种假设，即入侵 前列腺癌细胞对维生素的生化反应减弱 D与非癌前列腺癌细胞相比。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 结论：1.侵袭性前列腺癌细胞和非癌前列腺癌细胞； 确定这些受体水平和反应在不同男性之间有何不同 3个罹患前列腺癌风险不同的种族/民族。 为了实现这些目标，我们将：1.获取手术标本 来自黑人、白人和西班牙裔前列腺癌的新鲜前列腺组织 在宾夕法尼亚大学接受根治性前列腺切除术的患者 迈阿密/杰克逊纪念医疗中心；2.准备原代培养 每位患者的浸润性前列腺癌和非癌前列腺细胞 使用体外细胞侵袭试验；3.评估维生素D受体 通过报告基因检测维生素D受体的水平和功能。我们的 主要目标是确定维生素D敏感性是否与 侵袭性前列腺癌来源于非癌前列腺癌细胞。这项研究 可能最终允许确定那些前列腺癌 很可能是侵入性的。浸润性前列腺癌的鉴别诊断 是决定哪些男性应该接受积极治疗的关键 为了他们的疾病。

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.