Klein K G, Bouck N P
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611.
Cancer Genet Cytogenet. 1994 Apr;73(2):109-21. doi: 10.1016/0165-4608(94)90194-5.
Loss or inactivation of tumor suppressor genes has been implicated by indirect methods in the etiology of most human cancers. In the functional studies presented here, tumor suppressors on human chromosome 1 were investigated using microcell-mediated chromosome transfer. Translocated chromosomes from normal human cells representing most of 1q, or all of 1p and a small portion of 1q translocated onto the region of the X chromosome encoding HPRT, were transferred into human fibrosarcoma cell line HT1080. Analysis of HT1080 microcell hybrids showed a tumor suppressor activity associated with 1q. All HT1080 cells carrying transferred 1q in a ratio of 1:1 with the HT1080 genome showed a more flattened morphology and a reduced ability to form tumors in nude mice compared to parental HT1080 cells. Diploid HT1080 cells carrying a single extra 1q also had a longer population doubling time and showed a loss of ability to clone in soft agar. Tumors arose from 1q-containing clones with a longer latency period, and a large majority of the cells comprising these tumors had lost the transferred chromosome. These results indicate the presence on chromosome 1q23-qter of a tumor suppressor gene or genes that can act to suppress transformation of a human fibrosarcoma cell line.
通过间接方法已表明肿瘤抑制基因的缺失或失活与大多数人类癌症的病因有关。在本文所呈现的功能研究中，利用微细胞介导的染色体转移对人类1号染色体上的肿瘤抑制基因进行了研究。将代表大部分1q或全部1p以及1q一小部分的正常人类细胞的易位染色体转移到编码次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（HPRT）的X染色体区域，然后导入人类纤维肉瘤细胞系HT1080。对HT1080微细胞杂种的分析显示出与1q相关的肿瘤抑制活性。与亲代HT1080细胞相比，所有携带与HT1080基因组比例为1:1的转移1q的HT1080细胞表现出更扁平的形态以及在裸鼠中形成肿瘤的能力降低。携带单个额外1q的二倍体HT1080细胞也具有更长的群体倍增时间，并且在软琼脂中丧失了克隆能力。含有1q的克隆形成肿瘤的潜伏期更长，并且构成这些肿瘤的大多数细胞已经丢失了转移的染色体。这些结果表明在1q23 - qter染色体上存在一个或多个能够抑制人类纤维肉瘤细胞系转化的肿瘤抑制基因。
