The Fn14 immediate-early response gene is induced during liver regeneration and highly expressed in both human and murine hepatocellular carcinomas
The Fn14 immediate-early response gene is induced during liver regeneration and highly expressed in both human and murine hepatocellular carcinomas
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DOI：
10.1016/s0002-9440(10)64996-6
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发表时间：
2000-04-01
影响因子：
6
通讯作者：
Winkles, JA
中科院分区：
文献类型：
--
作者：
Feng, SLY;Guo, Y;Winkles, JA
多肽生长因子通过与特定的细胞表面受体结合来刺激哺乳动物细胞增殖，这种相互作用触发了许多生化反应，包括蛋白磷酸化级联的激活和特定基因的表达增强。我们已经确定了几个成纤维细胞生长因子（FGF）诱导的基因在小鼠MH 3 T3细胞，最近报道，其中之一，FGF诱导14（Fn 14）立即早期反应基因，预计编码一种新的，细胞表面定位的Ia型跨膜蛋白。在这里，我们报告说，人类Fn 14同源物位于染色体16p13.3和编码一个129个氨基酸的蛋白质与类似的82%的序列同一性的小鼠蛋白质。人Fn 14基因，像鼠Fn 14基因一样，在体外成纤维细胞的FGF、小牛血清或佛波酯处理后以升高的水平表达，并且在体内心脏和肾脏中以相对高的水平表达。我们还报告说，人Fn 14基因在正常肝组织中表达水平相对较低，但在肝癌细胞系和肝细胞癌标本中表达水平较高。此外，鼠Fn 14基因在体内肝再生过程中被快速诱导，并在c-myc/转化生长因子-α驱动和肝炎B病毒X蛋白驱动的肝癌发生转基因小鼠模型中发展的肝细胞癌结节中以高水平表达。这些结果表明，Fn 14可能在肝细胞生长控制和肝肿瘤中起作用。
Polypeptide growth factors stimulate mammalian cell proliferation by binding to specific cell surface receptors, This interaction triggers numerous biochemical responses including the activation of protein phosphorylation cascades and the enhanced expression of specific genes. We have identified several fibroblast growth factor (FGF)-inducible genes in murine MH 3T3 cells and recently reported that one of them, the FGF-inducible 14 (Fn14) immediate-early response gene, is predicted to encode a novel, cell surface-localized type Ia transmembrane protein. Here, we report that the human Fn14 homolog is located on chromosome 16p13.3 and encodes a 129-amino acid protein with similar to 82% sequence identity to the murine protein. The human Fn14 gene, like the murine Fn14 gene, is expressed at elevated levels after FGF, calf serum or phorbol ester treatment of fibroblasts in vitro and is expressed at relatively high levels in heart and kidney in vivo. We also report that the human Fn14 gene is expressed at relatively low levels in normal liver tissue but at high levels in liver cancer cell lines and in hepatocellular carcinoma specimens. Furthermore, the murine Fn14 gene is rapidly induced during liver regeneration in vivo and is expressed at high levels in the hepatocellular carcinoma nodules that develop in the c-myc/transforming growth factor-alpha-driven and the hepatitis B virus X protein-driven transgenic mouse models of hepatocarcinogenesis. These results indicate that Fn14 may play a role in hepatocyte growth control and Liver neoplasia.