Tumorigenicity and transcriptional modulation of c-myc and N-ras oncogenes in a human hepatoma cell line.
Tumorigenicity and oncogene expression were examined in HepG2 derived cells, a human hepatoma cell line. HepG2 cells and a single cell clonal HepG2 line, HLD2-6, were equally tumorigenic when injected s.c. into athymic nude mice. Cyclophosphamide pretreatment of both cell lines (500 micrograms cyclophosphamide/ml/two cell cycles) had no effect on tumor incidence or latency (P greater than 0.05). Tumors were nonencapsulated, highly invasive adenocarcinomas and were positive for gamma-glutamyltranspeptidase activity and bile production. Plasma from tumor-bearing mice was positive for human alpha-fetoprotein and negative for hepatitis B virus surface antigen as measured by radioimmunoassay. Two cell lines reestablished into tissue culture from HLD2-6 derived tumors had unaltered cell cycle times. Detailed in vitro translation analysis of RNA isolated from HLD2-6 derived cells and tumors were extremely similar to the translation products of RNA isolated from a normal human liver sample except for a Mr 53,000 polypeptide with an apparent charge shift. c-myc specific transcripts, when compared to a normal human liver sample, were increased in all HLD2-6 cell lines and tumors derived from HLD2-6 cells. This increase in c-myc expression could not be explained by gene amplification or hepatitis B virus integration. N-ras specific transcripts were not elevated in HLD2-6 cells grown in tissue culture but there was a selective increase of the 5.5-kilobase N-ras transcript in HLD2-6 derived tumors grown in nude mice. This increased 5.5-kilobase transcript did not remain elevated if the tumors were reestablished into tissue culture, suggesting some interaction with the host animal. c-Ha-ras expression could not be detected in any HLD2-6 derived tumor or cell line.
Huber
B E
BE
Dearfield
K L
KL
Williams
J R
JR
Heilman
C A
CA
Thorgeirsson
S S
SS
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009693:Nucleic Acid Hybridization; D009857:Oncogenes; D014158:Transcription, Genetic