DOWN REGULATION OF METASTASIS SUPPRESSOR GENE PREDICTING PROSTATE CANCER BEHAVIOR

目前，美国男性被诊断出的每四种癌症中就有一种是 起源于前列腺癌的。前列腺癌一旦转移，就是一种 没有根治方法的致命疾病 现在。由于这些事实，人们对……越来越感兴趣 积极筛查男性前列腺癌，以便及早 前列腺癌的检测可能会识别出1000万 美国男性体内的癌细胞在组织学上可检测到 他们的前列腺。据估计，大约7%(70万) 最终会死于这些癌症的进展 细胞。这提出了一个关键问题，即哪一个 其余93%(9,300,000)的男性患有非致命性但潜在的 改变生活的，组织学可检测到的前列腺癌 分成需要立即治疗与不治疗的患者。 通过这种组织学可检测的方法获得转移能力 前列腺癌细胞是建立在其基础上的明确标准 这样一种诊断分阶段的方法。因此，检测特定的 分子变化肯定与获得 前列腺癌细胞的转移能力可用于 结合组织学分级适当分期 从而使组织学上的患者个体化治疗 检测出前列腺癌。私家侦探实验室的研究表明 证明这种转移能力的获得是通过 前列腺癌细胞不仅涉及蛋白表达的增加 某些癌基因(S)但也降低了某些其他癌基因的表达 转移抑制基因(S)。因此，这一行动的具体目标是 项目是：1)确定染色体在 人类基因组中这些转移抑制基因(S)用于前列腺癌 癌症，2)克隆位于这些区域的表达基因(S) 人类特定的染色体区域，3)开发抗体 免疫细胞化学检测这些基因的表达缺失 前列腺癌和4)转移抑制基因产物 确定是否下调或缺乏其中任何一个的表达 在特异靶2中发现的基因(S)可用于预测 人前列腺癌的转移能力。使用这个 方法，至少有一个这种转移抑制基因(称为 KAI-1)已被鉴定、克隆并定位到人类染色体上 11p11.2因前列腺癌在前两年的孢子 支持。

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.