Guan Xin-Yuan, Fung Jackie M-W, Ma Ning-Fang, Lau Sze-Hang, Tai Lai-Shan, Xie Dan, Zhang Yu, Hu Liang, Wu Qiu-Liang, Fang Yan, Sham Jonathan S T
Department of Clinical Oncology, The University of Hong Kong, People's Republic of China.
Cancer Res. 2004 Jun 15;64(12):4197-200. doi: 10.1158/0008-5472.CAN-03-3747.
Amplification of 3q26 is one of the most frequent chromosomal alterations in many solid tumors, including ovarian, lung, esophageal, prostate, breast, and nasopharyngeal cancers. A candidate oncogene to eukaryotic initiation factor 5A2 (eIF-5A2), a member of eukaryotic initiation factor 5A subfamily, has been isolated from a frequently amplified region at 3q26.2. In this work, the tumorigenic ability of eIF-5A2 was demonstrated by anchorage-independent growth in soft agar and tumor formation in nude mice. Furthermore, antisense DNA against eIF-5A2 could inhibit cell growth in ovarian cancer cell line UACC-1598 with amplification of eIF-5A2 in form of double minutes. Cell growth rate in UACC-1598 was also inhibited when the expression level of EIF-5A2 was decreased by the reduction of the copy number of double minutes. The correlation of EIF-5A2 overexpression and clinical features of ovarian cancer was investigated using tissue microarray, and the result showed that eIF-5A2 overexpression was significantly associated with the advanced stage of ovarian cancer. These findings suggest that eIF-5A2 plays important roles in ovarian pathogenesis.
3q26扩增是许多实体瘤中最常见的染色体改变之一,这些实体瘤包括卵巢癌、肺癌、食管癌、前列腺癌、乳腺癌和鼻咽癌。真核起始因子5A亚家族成员真核起始因子5A2(eIF-5A2)作为一个候选癌基因,已从3q26.2处一个频繁扩增的区域中分离出来。在这项研究中,eIF-5A2的致瘤能力通过软琼脂中锚定非依赖性生长和裸鼠体内肿瘤形成得以证实。此外,针对eIF-5A2的反义DNA能够抑制卵巢癌细胞系UACC-1598的细胞生长,该细胞系以双微体形式存在eIF-5A2扩增。当双微体拷贝数减少导致EIF-5A2表达水平降低时,UACC-1598中的细胞生长速率也受到抑制。利用组织芯片研究了EIF-5A2过表达与卵巢癌临床特征的相关性,结果显示eIF-5A2过表达与卵巢癌晚期显著相关。这些发现表明eIF-5A2在卵巢癌发病机制中发挥重要作用。