Amphiregulin: a new growth factor in hepatocarcinogenesis.
Amphiregulin (AR) is a member of the epidermal growth factor family and a ligand of the epidermal growth factor receptor (EGFR). As other ligands of the EGFR, AR is synthesized as a precursor that is shed from the plasma membrane by metalloproteases. Hyperactive autocrine loops involving AR production have been described in a variety of tumors, and this growth factor is thought to play a non-redundant role in cancer development. AR expression is not detected in the normal liver, however it is readily induced during acute liver injury and behaves as a potent pro-regenerative and survival factor. Increased AR expression is also detected in human chronic liver injury (liver cirrhosis), which is considered a pre-neoplastic condition. Recent evidences suggest that AR can play a unique role in liver tumorigenesis and in the maintenance of the neoplastic phenotype of hepatocarcinoma cells. In this review, we summarize some aspects of AR patho-biology and the rationale behind its definition as a novel target in hepatocarcinoma therapy.
Berasain
C
C
Division of Hepatology and Gene Therapy, CIMA, Universidad de Navarra, Pamplona, Spain. cberasain@unav.es
Castillo
J
J
Perugorría
M J
MJ
Prieto
J
J
Avila
M A
MA
D066258:Amphiregulin; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D066255:EGF Family of Proteins; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D015398:Signal Transduction
C587848:AREG protein, human; D066258:Amphiregulin; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins