DOWN REGULATION OF METASTASIS SUPPRESSOR GENE PREDICTING PROSTATE CANCER BEHAVIOR

预测前列腺癌行为的转移抑制基因的下调

• 批准号: 6102874
• 负责人: JOHN Tod ISAACS
• 金额: --
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-28 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6102874
• 关键词: antitumor antibody; athymic mouse; gene expression; genetic mapping; histopathology; human genetic material tag; human tissue; immunocytochemistry; male; metastasis; molecular cloning; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; neoplasm /cancer genetics; prostate neoplasms; tumor suppressor genes

Presently, one of every four cancers diagnosed in American males is of prostatic origin. Once prostatic cancer metastasizes, it is a fatal disease for which curative therapy is not available presently. Because of these facts, there is a growing interest in aggressive screening of men for prostate cancer to allow early detection of prostatic could potentially identify 10 million American men with cancer cells histologically detectable within their prostates. It is estimated that approximately 7% (700,000) of these men will eventually die from progression of these cancer cells. This raises the critical question as to which of the remaining 93% (9,300,000) of men with nonlethal, but potentially life-altering, histologically detectable prostatic cancer to be substaged into those requiring immediate therapy vs no treatment. Acquisition of metastatic ability by such histologically detectable prostatic cancer cells is a definitive criterion upon which to base such a diagnostic substaging method. Thus, detection of specific molecular changes definitely associated with acquisition of metastatic ability by prostatic cancer cells could be used in combination with histological grading to appropriately substage and thus individualized the treatment of patients with histologically detected prostatic cancer. Studies in the PI's laboratory have demonstrated that acquisition of such metastatic ability by prostatic cancer cells involves not only increased expression of certain oncogene(s) but also decreased expression of certain other metastasis suppressor gene(s). Thus, the specific aims of this project are: 1) to determine the chromosomal locations within the human genome of these metastasis suppressor gene(s) for prostatic cancer, 2) to clone the expressed gene(s) located within these specific human chromosomal regions, 3) to develop antibodies for the immunocytochemical detection of loss of expression of these metastases suppressor gene products by prostatic cancers and 4) to determine if down-regulation or lack of expression of any of these gene(s) identified in specific aim 2 can be used to predict the metastatic ability of human prostatic cancers. Using this approach, at least one such metastatic suppressor gene (termed the Kai-1) has been identified, cloned, and mapped to human chromosome 11p11.2 for prostatic cancer during the previous 2 years of SPORE support.

目前，在美国男性中诊断出的四分之一的癌症是 前列腺起源。 前列腺癌一旦转移， 无法治愈的致命疾病 现在。 由于这些事实， 积极筛查男性前列腺癌， 检测前列腺可能会识别1000万 美国男子与癌细胞组织学检测内 前列腺 据估计，约7%（70万） 这些人最终会死于这些癌症的进展 细胞 这就提出了一个关键问题， 其余93%（9，300，000）的男性患有非致命性，但可能 改变生活的，组织学上可检测的前列腺癌， 亚阶段分为需要立即治疗与不需要治疗的患者。 通过这种组织学上可检测到的转移能力的获得 前列腺癌细胞是一个决定性的标准， 这种诊断子阶段方法。 因此，检测特定 分子变化肯定与获得 前列腺癌细胞的转移能力可用于 结合组织学分级进行适当的分期， 从而使患者的组织学治疗个性化， 检测出前列腺癌 PI实验室的研究 证明了这种转移能力的获得， 前列腺癌细胞不仅涉及 某些癌基因的表达也降低， 转移抑制基因。 因此，这一具体目标 项目是：1）确定染色体内的位置， 这些前列腺转移抑制基因人类基因组 癌症，2）克隆位于这些细胞内的表达基因， 特定的人类染色体区域，3）开发抗体， 免疫细胞化学检测这些表达的缺失， 前列腺癌的转移抑制基因产物和4） 确定是否下调或缺乏表达的任何这些 在具体目标2中鉴定的基因可用于预测 人前列腺癌的转移能力。 使用此 方法，至少一个这样的转移抑制基因（称为转移抑制基因）， Kai-1）已被鉴定、克隆并定位到人类染色体上 11p11.2前列腺癌在过去2年的SPORE 支持.