MECHANISMS OF PROSTATE EPITHELIAL CELL TRANSFORMATION

描述：本提案的总体目标是确定 成年人非肿瘤性前列腺 上皮细胞被驱使向越来越恶性的表型发展。 研究发现与以下疾病相关的特定细胞遗传学改变： 具有SV 40大T抗原的致瘤或转移能力 永生化人前列腺上皮细胞（SV 40 T PEC）在无胸腺裸 小鼠为研究转化机制提供了新的途径。 在这 建议，要测试的假设是，染色体16和/或19 含有一个或多个抑制致瘤性和/或转移的基因。 其具体目的是：（1）进一步划定最小损失区域 杂合性（洛）发生在染色体16和19，因为这些细胞 进展;（2）确定是否恢复正常染色体剂量 通过微细胞介导的转移：（a）完整的正常人染色体 16，或（B）染色体19进入适当的克隆将抑制肿瘤 无胸腺裸鼠中的发病率、生长速率和/或转移;（3） 利用他们独特的系统来识别16号染色体上的最小区域 和/或具有功能性肿瘤抑制活性的19个。 这些研究 将有助于了解最常见的肿瘤发生在 美国男人 这可能为改进诊断带来新的机会， 预后评估，或治疗干预的疾病，没有 满意的治疗方案。

DESCRIPTION: The overall objective of this proposal is to identify molecular genetic mechanisms by which adult human non-neoplastic prostate epithelial cells are driven towards increasingly malignant phenotypes. Investigation of specific cytogenetic alterations found to be associated with the tumorigenic or metastatic capacity of SV40 large T antigen immortalized human prostate epithelial cells (SV40T PEC) in athymic nude mice provides a novel way to study mechanism of transformation. In this proposal, the hypothesis to be tested is that chromosomes 16 and/or 19 contain one or more genes that suppress tumorigenicity and/or metastasis. The specific aims are: (1) to further delineate the minimal regions of loss of heterozygosity (LOH) occurring on chromosomes 16 and 19 as these cells progress; (2) to determine whether restoration of normal chromosome dosage by microcell mediated transfer of: (a) an intact normal human chromosome 16, or (b) chromosome 19 into appropriate clones will suppress tumor incidence, growth rate, and/or metastasis in athymic nude mice; (3) to exploit their unique system to identify the smallest areas on chromosomes 16 and/or 19 that harbor functional tumor suppressor activity. These studies will facilitate understanding of the most common tumor occurring among American men. This may lead to new opportunities for improved diagnosis, prognostic assessment, or therapeutic intervention for a disease having no satisfactory treatment options.