Forced expression of hepatocyte‐specific fibroblast growth factor 21 delays initiation of chemically induced hepatocarcinogenesis

摘要: Inappropriate fibroblast growth factor (FGF) signaling is involved in most tissue-specific pathologies including cancer. Previously we showed that inappropriate expression and chronic activity of FGF receptor (FGFR) 1 hepatocytes accelerated diethylnitrosamine (DEN)-initiated hepatocarcinogenesis. Here although widely expressed FGF1 FGF2 are frequently upregulated hepatocellular carcinoma (HCC), germline deletion both had no effect on DEN-initiated Thus overexpression or may be a consequence rather than contributor to hepatoma progression. FGF21 the first 22 homologues whose has been reported preferentially liver. We similar FGF2, mRNA was neoplastic regenerating liver after partial hepatectomy (PH) CCl4 administration. In situ hybridization analysis confirmed contrast limited hepatocytes. Forced by gene targeting apparent impact normal development compensatory response injury. Surprisingly, delayed appearance DEN-induced tumors. At 8 10 mo, only 10% 30% transgenic mice, respectively, developed adenomas compared 50% (all adenomas) 80% (60% adenoma/20% HCC) wild-type (WT) mice. However, incidence burden HCC at mo later equal WT propose delay through activation resident hepatocyte FGFR4 early times, but counteracts acceleration progression interaction with ectopic FGFR1 once it appears cells. This indicates dual function reflect changes FGFR isotype during differentiated