Characterization of HLS5, a novel tumor suppressor gene

HLS5是我们实验室最近发现的一种新基因。初步研究表明，HLS5类似于一个充当DNA调节器的基因家族。我们发现HLS5位于8号染色体上一个在人类肿瘤中经常缺失的区域，提示HLS5是一种新的抑癌基因。该基因的破坏可能导致某些类型的癌症(特别是乳腺癌和前列腺癌)的形成。支持HLS5是肿瘤抑制基因的其他证据来自它与这些伙伴分子相关的蛋白质，这些蛋白质参与DNA修复或DNA调控。当我们将HLS5引入癌细胞时，它减缓了它们的生长，降低了它们形成肿瘤的能力。因此，该项目的目的是对HLS5基因进行详细分析，并确定其蛋白质产物的功能。这项研究将采用多种方法相结合的方法。我们将：(I)改变HLS5在癌细胞中的表达量，(Ii)鉴定与HLS5结合的蛋白质，(Iii)确定HLS5在细胞中的定位，(Iv)分析缺乏HLS5基因的小鼠，(V)评估HLS5与人类白血病的关系，(Vi)分析产生蛋白质的HLS5信使RNA，以及(Vii)确定HLS5蛋白质的结构。这些研究应该为HLS5如何发挥作用以及它在癌症形成中的作用提供有价值的信息。

HLS5 is a novel gene that we recently discovered in our laboratory. Preliminary investigations suggest that HLS5 is similar to a family of genes which act as DNA regulators. We have shown that HLS5 is found on a region of chromosome 8 which is often deleted in human cancers, suggesting that HLS5 is a new tumour suppressor gene i.e.. damage to this gene may be responsible for the formation of certain types of cancer (specifically breast and prostate). Other evidence to support the claim that HLS5 is a tumour suppressor gene comes from the proteins it associates with these partner molecules are involved in DNA repair or DNA regulation. When we introduced HLS5 into cancer cells, it slowed their growth and reduced their ability to form tumours. The aim of this project therefore, is to undertake a detailed analyses of the HLS5 gene and to determine the function of its protein product. A combination of approaches will be used in this study. We will: (i) alter the amount of HLS5 expression in cancer cells, (ii) characterize the proteins which bind to HLS5, (iii) determining where HLS5 localizes in the cell, (iv) analyze mice with lack the gene for HLS5, (v) assess the involvement of HLS5 in a human leukemia (vi) analyze HLS5 messenger RNA which produces the protein, and (vii) determining the structure of HLS5 protein. These studies should provide valuable information on how HLS5 functions, as well as its role in cancer formation.