Department of Pediatric Gastroenterology, Chang Gung Children's Hospital, and Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, ROC.
Anticancer Res. 2011 Jun;31(6):2037-44.
Since Rho-mediated signaling can regulate liver cancer cell proliferation, amino acid sequence changes of its downstream targets, actins, might alter the properties of cell growth. Here, we investigated the function of a novel class of actins, named κ-actins, in hepatocellular carcinoma (HCC).
Alexander cells overexpressing an HCC-derived κ-actin (Alex-κ cells) were established to study growth property changes. κ-actin expression was also determined in tumor and noncancerous tissues from 72 HCC patients. Survival analysis was conducted to evaluate the prognostic predictive value of κ-actin expression.
Phylogenetic analysis showed that κ-actin sequences constituted 94.7% and 17.6% of actin transcripts in Alex-κ and naive Alexander cells, respectively. Alex-κ cells exhibited serum-independent cell growth with increased anchorage-independent colony formation and BrdU incorporation upon serum deprivation. Cox proportional hazard analysis showed that κ-actin expression in both cancerous and noncancerous tissues predicted poorer postoperative disease-free survival (p=0.004).
Overexpression of κ-actin altered growth properties of hepatoma cells, contributing to poor postoperative prognosis.
由于 Rho 介导的信号转导可以调节肝癌细胞的增殖，其下游靶标肌动蛋白的氨基酸序列变化可能改变细胞生长的特性。在这里，我们研究了一类新型肌动蛋白，称为 κ-肌动蛋白，在肝细胞癌 (HCC) 中的功能。
建立了表达 HCC 衍生 κ-肌动蛋白 (Alex-κ 细胞) 的 Alexander 细胞系，以研究生长特性的变化。还检测了 72 例 HCC 患者肿瘤和非癌组织中的 κ-肌动蛋白表达。进行生存分析以评估 κ-肌动蛋白表达的预后预测价值。
系统发育分析显示，κ-肌动蛋白序列分别构成 Alex-κ 和未处理的 Alexander 细胞中肌动蛋白转录本的 94.7%和 17.6%。Alex-κ 细胞在血清饥饿时表现出血清非依赖性细胞生长，增加了锚定非依赖性集落形成和 BrdU 掺入。Cox 比例风险分析表明，癌组织和非癌组织中 κ-肌动蛋白的表达均预示着术后无病生存率较差（p=0.004）。
κ-肌动蛋白的过表达改变了肝癌细胞的生长特性，导致术后预后不良。
