The Fn14 immediate-early response gene is induced during liver regeneration and highly expressed in both human and murine hepatocellular carcinomas

Polypeptide growth factors stimulate mammalian cell proliferation by bindin g to specific cell surface receptors, This interaction triggers numerous bi ochemical responses including the activation of protein phosphorylation cas cades and the enhanced expression of specific genes. We have identified sev eral fibroblast growth factor (FGF)-inducible genes in murine MH 3T3 cells and recently reported that one of them, the FGF-inducible 14 (Fn14) immedia te-early response gene, is predicted to encode a novel, cell surface-locali zed type Ia transmembrane protein. Here, we report that the human Fn14 homo log is located on chromosome 16p13.3 and encodes a 129-amino acid protein w ith 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 expre ssed 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 li ver tissue but at high levels in liver cancer cell lines and in hepatocellu lar carcinoma specimens. Furthermore, the murine Fn14 gene is rapidly induc ed during liver regeneration in vivo and is expressed at high levels in the hepatocellular carcinoma nodules that develop in the c-myc/transforming gr owth factor-alpha-driven and the hepatitis B virus X protein-driven transge nic mouse models of hepatocarcinogenesis. These results indicate that Fn14 may play a role in hepatocyte growth control and Liver neoplasia.