Yoshida B A, Chekmareva M A, Wharam J F, Kadkhodaian M, Stadler W M, Boyer A, Watabe K, Nelson J B, Rinker-Schaeffer C W
Department of Surgery, University of Chicago, IL, USA.
In Vivo. 1998 Jan-Feb;12(1):49-58.
Prostate cancers account for 43% of all cancers diagnosed in American men. It is estimated that in 1996, 317,000 new cases of prostate cancer were diagnosed and 41,000 men died of the disease. The challenge of treating prostate cancer lies in accurately distinguishing those histologically-localized cancers which will complete metastatic progression from those that will remain indolent. At this time, we lack appropriate histological markers to make such distinctions, therefore, it is often difficult to accurately predict the clinical course of an individual patient's disease. There is growing evidence that a critical event in the progression of a tumor cell from a non-metastatic to metastatic phenotype is the loss of function of metastasis-suppressor genes. These genes specifically suppress the ability of a cell to metastasize. Work from several groups has demonstrated that human chromosomes 8, 10, 11 and 17 encode prostate cancer metastasis suppressor activities. As a result of these efforts the first prostate cancer metastasis-suppressor gene, KAI1, was identified and mapped to the p11-2 region of chromosome 11. In subsequent studies, an additional gene encoded by the same region, CD44 was also determined to have metastasis-suppressor activity. Recent studies have shown a correlation between decreased expression of KAI1 and CD44 and an increased malignant potential of prostate cancers. It is anticipated that the identification of other metastasis suppressor genes may allow for the development of diagnostic markers useful in the clinical substaging of individual tumors. This manuscript is intended to present our perspective on the importance of these genes in the understanding of prostate cancer progression. More importantly, we present new findings from our laboratory's effort to identify the metastasis-suppressor genes encoded by human chromosome 17. Specifically we report the strategy currently being used to evaluate a series of candidate genes and the approach being utilized to pinpoint the metastasis-suppressor region on human chromosome 17.
前列腺癌占美国男性确诊癌症总数的43%。据估计，1996年有31.7万例新的前列腺癌病例被确诊，4.1万名男性死于该疾病。治疗前列腺癌的挑战在于准确区分那些组织学上局限的癌症，哪些会发展为转移性癌症，哪些会保持惰性。目前，我们缺乏合适的组织学标记来进行这种区分，因此，通常很难准确预测个体患者疾病的临床进程。越来越多的证据表明，肿瘤细胞从非转移性表型转变为转移性表型的一个关键事件是转移抑制基因功能的丧失。这些基因特异性地抑制细胞转移的能力。多个研究小组的工作表明，人类染色体8、10、11和17编码前列腺癌转移抑制活性。由于这些努力，第一个前列腺癌转移抑制基因KAI1被鉴定出来，并定位到染色体11的p11-2区域。在随后的研究中，同一区域编码的另一个基因CD44也被确定具有转移抑制活性。最近的研究表明，KAI1和CD44表达降低与前列腺癌恶性潜能增加之间存在关联。预计其他转移抑制基因的鉴定可能有助于开发用于个体肿瘤临床亚分期的诊断标记。本手稿旨在阐述我们对于这些基因在理解前列腺癌进展中的重要性的观点。更重要的是，我们展示了我们实验室在鉴定人类染色体17编码的转移抑制基因方面的新发现。具体来说，我们报告了目前用于评估一系列候选基因的策略，以及用于确定人类染色体17上转移抑制区域的方法。
