He Hua, Dai Fangyan, Yu Long, She Xingyu, Zhao Yong, Jiang Jianmin, Chen Xiaosong, Zhao Shouyuan
State Key Laboratory of Genetic Engineering, Group of Liver Cancer Research, Institute of Genetics, School of Life Science, Fudan University, 220 Handan Road, Shanghai 200433, PR China.
Gene Expr. 2002;10(5-6):231-42. doi: 10.3727/000000002783992406.
Digestion and detoxification are the two most important functions of the liver, and liver cells always keep a high metabolism level and active vesicular traffic. The malfunction of the vesicular traffic system might be a cause of the abnormal biological behavior of cancerous liver cells. The Ras superfamily is known to regulate various steps of vesicular traffic in eukaryotic cells. It would be significant to determine the change of vesicular transport molecules such as the members of Ras superfamily in carcinogenesis of liver cells. In the present study, we have cloned nine novel genes encoding human small GTPases: RAB1B, RAB4B, RAB10, RAB22A, RAB24, RAB25 ARL5, SARA1, and SARA2, among which the former six belong to the RAB family and the latter three belong to the ARF/SAR1 family. The identification of these new genes has greatly enlarged the pool of the Ras superfamily. It is interesting to find that they are upregulated in most of the 11 hepatocellular carcinoma and 1 cholangiohepatoma cases. Furthermore, the expression in 16 normal human adult tissues, the chromosome loci, and the gene structures of the nine genes are also described. The above findings could be valuable for understanding the vesicular transport system and elucidating the molecular basis of liver cancer carcinogenesis.
消化和解毒是肝脏的两个最重要功能，肝细胞始终保持高代谢水平和活跃的囊泡运输。囊泡运输系统的功能障碍可能是肝癌细胞异常生物学行为的一个原因。已知Ras超家族调节真核细胞中囊泡运输的各个步骤。确定诸如Ras超家族成员等囊泡运输分子在肝细胞癌变过程中的变化具有重要意义。在本研究中，我们克隆了九个编码人类小GTP酶的新基因：RAB1B、RAB4B、RAB10、RAB22A、RAB24、RAB25、ARL5、SARA1和SARA2，其中前六个属于RAB家族，后三个属于ARF/SAR1家族。这些新基因的鉴定极大地扩大了Ras超家族的基因库。有趣的是，发现在11例肝细胞癌和1例胆管肝癌病例中，它们大多呈上调状态。此外，还描述了这九个基因在16种正常成人组织中的表达、染色体定位和基因结构。上述发现对于理解囊泡运输系统和阐明肝癌发生的分子基础可能具有重要价值。
