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


CONCLUSIONS
The expression of exogenous PDX-1 is not sufficient to induce relatively mature hepatocytes differentiating into insulin-producing cells.
Lu
Shun
S
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, 38 Xue Yuan Road, Haidian District, Beijing 100083, China.
Wang
Wei-Ping
WP
Wang
Xiao-Fei
XF
Zheng
Zong-Mei
ZM
Chen
Ping
P
Ma
Kang-Tao
KT
Zhou
Chun-Yan
CY
D000818:Animals; D006528:Carcinoma, Hepatocellular; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D017690:Cell Transplantation / Q000379:methods*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000628:therapy*; D022781:Hepatocytes / Q000166:cytology*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology*; D008114:Liver Neoplasms, Experimental; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection
D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein