GENETIC LOCI ASSOCIATED WITH PROSTATE CANCER DEVELOPMENT

与前列腺癌发生相关的基因位点

• 批准号: 3549873
• 负责人: JAMES V TRICOLI
• 金额: $ 12.48万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-17 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3549873
• 关键词: African American; DNA methylation; chromosome deletion; cooperative study; gel electrophoresis; gene expression; gene mutation; genetic markers; human age group; human subject; immunocytochemistry; male; molecular oncology; neoplasm /cancer genetics; northern blottings; nucleic acid probes; polymerase chain reaction; prostate neoplasms; racial /ethnic difference; regulatory gene; southern blotting; tumor suppressor genes

Loss of heterozygosity for a number of chromosomal regions and the RB and P53 suppressor genes has been observed in human prostate tumors. However, these alterations are not yet sufficiently well defined to associate specific chromosomal loci with prostate malignancy. Our goal is to identify chromosomal loci associated with the malignant phenotype which provide a genetic basis for understanding the occurrence and clinical manifestations of this disease. We will focus on chromosomal regions previously identified as candidates for involvement in prostate cancer (8p, 10q, 10p, 16q, Y). This will be accomplished using DNA probes available for these chromosomal regions and FIGE gel, southern and PCR analysis of DNA from human prostate tumors and normal prostate or WBC DNA. These studies will include analysis of the RB-1 and P53 genes at the DNA, RNA and protein level. Efforts will be made to demonstrate the presence of defined chromosomal deletions associated with prostate cancers and to characterize defects in the RB-1 and P53 suppressor genes and their products. We will expand our previous studies on the altered expression of Y-encoded genes in prostate tumors by examining the expression of two important regulatory genes, ZFY and SRY, in tumor and normal tissues. This will include correlating gene expression with clinical parameters and gene methylation patterns. Finally, molecular data from these studies will be correlated with information on the race and age of individuals and the clinical behavior of the tumor. This effort is directed toward identifying specific genetic loci which can be used as markers for, and provide a genetic basis toward, understanding the ethnic and age bias observed in this disease, and that can distinguish localized from metastatic disease. These studies are a first step in defining the chromosomal regions associated with prostate cancer and toward identifying specific genetic loci which participate in the development of the disease.

许多染色体区域以及 RB 和 RB 杂合性丢失 P53 抑制基因已在人类前列腺肿瘤中观察到。 然而，这些改变尚未得到充分定义 将特定染色体位点与前列腺恶性肿瘤相关联。我们的目标是 识别与恶性表型相关的染色体位点 这为理解其发生和发生提供了遗传基础 本病的临床表现。 我们将重点关注染色体 先前确定为涉及前列腺的候选区域 癌症（8p、10q、10p、16q、Y）。 这将通过 DNA 来完成 可用于这些染色体区域和FIGE凝胶、南部和 对来自人类前列腺肿瘤和正常前列腺或 WBC 的 DNA 进行 PCR 分析 脱氧核糖核酸。 这些研究将包括对 RB-1 和 P53 基因的分析 DNA、RNA 和蛋白质水平。 将努力示范 存在与前列腺相关的确定的染色体缺失 癌症并表征 RB-1 和 P53 抑制基因的缺陷 和他们的产品。 我们将扩展我们之前对改变的研究 通过检查前列腺肿瘤中 Y 编码基因的表达 两个重要的调控基因 ZFY 和 SRY 在肿瘤和 正常组织。 这将包括将基因表达与 临床参数和基因甲基化模式。 最后，分子 这些研究的数据将与比赛信息相关联 个体的年龄和肿瘤的临床行为。 这 努力的方向是确定特定的遗传位点，这些位点可以 用作理解的标记并提供遗传基础 在这种疾病中观察到的种族和年龄偏见，这可以 区分局限性和转移性疾病。 这些研究是首次 定义与前列腺癌相关的染色体区域的步骤 并确定参与该过程的特定遗传位点 疾病的发展。