Heterogeneity in predisposition of hepatic cells to be induced into pancreatic endocrine cells by PDX-1.

AIM: The role of Pancreatic and Duodenal Homeobox-1 (PDX-1) as a major regulator of pancreatic development determines the function and phenotype of beta cell. In this study, potential plasticity of liver cells into pancreatic endocrine cells induced by PDX-1 was evaluated. METHODS: Human hepatoma cell line HepG2 was stably transfected with mammalian expression plasmid pcDNA3-PDX encoding human PDX-1 gene. Ectopic expression of PDX-1 and insulin were detected by RT-PCR, Western blot and/or immunostaining. PDX-1(+) HepG2 cells were transplanted under renal capsule of STZ-induced diabetic nude mice (n = 16) to examine the inducing effect in vivo. RESULTS: Exogenous PDX-1 transgene was proved to express effectively in HepG2 cell at both mRNA and protein levels. The expression of endogenous insulin and some beta cell-specific differentiation markers and transcription factors were not induced in PDX-1(+) HepG2 cells. When transplanted under renal capsule of STZ-induced diabetic nude mice, PDX-1(+) HepG2 cells did not generate insulin-producing cells. These data indicated that stable transfected PDX-1 could not convert hepatoma cell line HepG2 to pancreatic cells in vitro or in vivo. Mature hepatocytes might need much more complicated or rigorous conditions to be shifted to insulin-producing cells. CONCLUSION: The expression of exogenous PDX-1 is not sufficient to induce relatively mature hepatocytes differentiating into insulin-producing cells. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.