Absence of oncogenic transformation despite acquisition of cytogenetic aberrations in long-term cultured telomerase-immortalized human fetal hepatocytes.
As a culture model to study hepatocarcinogenesis, telomerase-immortalized human fetal hepatocytes were monitored for karyotype changes evolving in long-term culture and development of functional defects in DNA damage response. G-banding revealed acquisition of characteristic karyotype abnormalities, e.g., trisomy 7 and monosomy X, in two independently immortalized and cultured populations after 80-100 population doublings. Interestingly, the detected aneuploidies resemble some of the genetic events observed in hepatocellular cancer. However, these genetic changes were not sufficient to induce oncogenic transformation reflected by absence of anchorage-independent growth. Furthermore, long-term cultured telomerase-immortalized cells preserved p53 expression levels and effective p53-mediated damage response.
Haker
Björn
B
Department of Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
Fuchs
Sigrid
S
Dierlamm
Judith
J
Brümmendorf
Tim H
TH
Wege
Henning
H
D015153:Blotting, Western; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D016922:Cellular Senescence; D002869:Chromosome Aberrations; D004249:DNA Damage; D005333:Fetus; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007621:Karyotyping; D009154:Mutation; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D014161:Transduction, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016159:Tumor Suppressor Protein p53; C509186:TERT protein, human; D019098:Telomerase