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Division of Cell Biology, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709
A plasmid containing the CCAAT/enhancer-binding protein (C/EBP
) gene transcriptionally controlled by the metallothionein promoter was constructed. The gene was transfected into the human hepatocellular carcinoma cell lines Hep3B and HepG2. When cultured in vitro in the presence of 100 µM ZnSO4, C/EBP expression caused reversible growth arrest. In soft agar clonogenic assays, C/EBP expression decreased both the colony size and the total number of colonies compared with zinc-free controls. C/EBP expressing cells s.c. implanted in Cd-1 nu/nu mice were essentially nontumorigenic, whereas C/EBP tumor cells implanted into immunodeficient SCID mice demonstrated a significantly delayed time of tumor appearance compared with cells transfected with a vector control plasmid. These studies suggest that the expression of endogenous genes normally associated with a quiescent, differentiated state, such as C/EBP, can result in impaired proliferative activity and suppressed tumorigenicity of hepatoma cell lines.
1 To whom reprint requests should be addressed, at Division of Cell Biology, Wellcome Research Laboratories, 3030 Cornwallis Road, Research Triangle Park, NC 27709. Phone: (919)-483-1262; Fax: (919)-315-3321.
Received 6/27/95. Accepted 1/ 2/96.
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