Characterization of trans-immortalized hepatic cell lines established from transgenic mice.
Hepato-specific regulatory (promoter/enhancer) DNA sequences were used for targeting the expression of onc genes, such as murine c-myc and Simian Virus 40 T Antigen, to hepatocytes of transgenic mice which subsequently developed hepatocellular carcinomas after a variable period of time (depending on the type of onc gene employed). Several trans-immortalized cell lines were established and compared with respect to the expression of adult hepatic markers and response to growth factors. Despite the morphological differences observed between trans-hepatomas, owing to the expression of the two different onc genes, all tumor-derived cell lines behaved in a comparable fashion during long-term culture displaying an adult hepatic phenotype for at least 40 passages. They differed, however, in response to epidermal growth factor. When the gene coding for human alpha 1-antitrypsin was placed under the control of the same hepato-specific promoter/enhancer, high levels of the human recombinant protein could be harvested from the supernatants of trans-hepatoma-derived cell lines.
Perraud
F
F
Transgene S.A., Strasbourg, France.
Dalemans
W
W
Gendrault
J L
JL
Dreyer
D
D
Ali-Hadji
D
D
Faure
T
T
Pavirani
A
A
D000209:Acute-Phase Proteins / Q000235:genetics; D000418:Albumins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression; D008099:Liver / Q000166:cytology*; D008114:Liver Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D000515:alpha 1-Antitrypsin / Q000235:genetics; D000509:alpha-Fetoproteins / Q000235:genetics
D000209:Acute-Phase Proteins; D000418:Albumins; D000952:Antigens, Polyomavirus Transforming; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin; D000509:alpha-Fetoproteins; D004815:Epidermal Growth Factor