title: Developmental Stage-Specific Embryonic Induction of HepG2 Cell Differentiation.
abstract: BACKGROUND
  Although hepatocellular carcinoma cells can sometimes undergo differentiation in an embryonic microenvironment, the mechanism is poorly understood.
  
  
  OBJECTIVE
  The developmental stage-specific embryonic induction of tumor cell differentiation was investigated.
  
  
  METHODS
  Both chick and mouse liver extracts and hepatoblast-enriched cells at different developmental stages were used to treat human hepatoma HepG2 cells, and the effects on the induction of differentiation were evaluated. The nuclear factors controlling differentiation, hepatocyte nuclear factor (HNF)-4α, HNF-1α, HNF-6 and upstream stimulatory factor-1 (USF-1), and the oncogene Myc and alpha-fetoprotein (AFP) were measured. HNF-4α RNA interference was used to verify the role of HNF-4α. Embryonic induction effects were further tested in vivo by injecting HepG2 tumor cells into immunodeficient nude mice.
  
  
  RESULTS
  The 9-11-days chick liver extracts and 13.5-14.5-days mouse hepatoblast-enriched cells could inhibit proliferation and induce differentiation of HepG2 cells, leading to either death or maturation to hepatocytes. The maturation of surviving HepG2 cells was confirmed by increases in the expressions of HNF-4α, HNF-1α, HNF-6, and USF-1, and decreases in Myc and AFP. The embryonic induction of HepG2 cell maturation could be attenuated by HNF-4α RNA interference. Furthermore, the 13.5-days mouse hepatoblast culture completely eliminated HepG2 tumors with inhibited Myc and induced HNF-4α, confirming this embryonic induction effect in vivo.
  
  
  CONCLUSIONS
  This study demonstrated that developmental stage-specific embryonic induction of HepG2 cell differentiation might help in understanding embryonic differentiation and oncogenesis.
authors.affiliation: Department of Molecular Biology, Hebei Key Lab of Laboratory Animal, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, No. 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zong
authors.affiliation: Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, No. 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, No. 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China.
authors.forename: Mengxuan
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, No. 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, No. 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China. qijinsheng777@163.com.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Biochemistry, Hebei Key Laboratory of Medical Biotechnology, Hebei Medical University, No. 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D002642:Chick Embryo; D004627:Embryonic Induction; D056945:Hep G2 Cells / Q000502:physiology*; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism; D006801:Humans; D008110:Liver Extracts; D051379:Mice
chemical_list: C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D008110:Liver Extracts
keywords: Embryonic induction; HepG2 cells; Hepatocellular carcinoma; Hepatocyte nuclear factor-4 alpha