title: Absence of oncogenic transformation despite acquisition of cytogenetic aberrations in long-term cultured telomerase-immortalized human fetal hepatocytes.
abstract: 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.
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Haker
authors.forename: Sigrid
authors.initials: S
authors.lastname: Fuchs
authors.forename: Judith
authors.initials: J
authors.lastname: Dierlamm
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.forename: Henning
authors.initials: H
authors.lastname: Wege
mesh_terms: 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
chemical_list: D016159:Tumor Suppressor Protein p53; C509186:TERT protein, human; D019098:Telomerase