Modulating IGFBP-3 expression by trichostatin A: potential therapeutic role in the treatment of hepatocellular carcinoma.
The Hep3B cell line analyzed in the present study is a widely used in vitro model in studies characterizing pathogenetic, functional, and therapeutic aspects of human hepatocellular carcinoma (HCC). Here we have determined the chromosomal composition using a combination of cytogenetic techniques. In agreement with the original description for this cell line, Hep3B was found to have a hypotriploid chromosome content carrying 59-63 chromosomes and no cytogenetic differences were demonstrated between early and late passages suggesting that this cell line has remained stable after repeated subculturing. Mutations and alterations of the IGF-axis as well as of chromosome 1p34, where the genes for histone deacetylase 1 (HDAC1) and transforming growth factor beta receptor interacting protein-1 (TRIP-1) map, are frequent events in hepatocarcinogenesis. This study characterizes the Hep3B cell line in detail at the karyotypic level, using comparative genomic hybridization (CGH), spectral karyotyping (SKY), G-banding and FISH techniques. We have also examined the effects of the histone deacetylase inhibitor trichostatin A (TSA) on members of the IGF-axis, and analysed them with regard to the karyotype. The results show that expression of one member of the IGF-axis, IGFBP-3, is greatly upregulated by treatment of Hep3B cells with TSA. As IGFBP-3 has been shown to induce apoptosis, these results suggest a possible use for histone deacetylase inhibitors and/or IGFBP-3 in the treatment of HCC.
Gray
S G
SG
Laboratory for Molecular Development and Tumor Biology, Experimental Alcohol and Drug Addiction Research Section, Department of Clinical Neuroscience, Karolinska Hospital, CMM, L8:01, S-171 76 Stockholm, Sweden.
Kytola
S
S
Lui
W O
WO
Larsson
C
C
Ekstrom
T J
TJ
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000628:therapy; D002871:Chromosome Banding; D002874:Chromosome Mapping; D039621:Eukaryotic Initiation Factor-3; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D017404:In Situ Hybridization, Fluorescence; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D007621:Karyotyping; D008113:Liver Neoplasms / Q000235:genetics* / Q000628:therapy; D011003:Ploidies; D011506:Proteins / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000187:drug effects; D012260:Ribonucleases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D039621:Eukaryotic Initiation Factor-3; D006877:Hydroxamic Acids; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D011506:Proteins; D017527:Receptor, IGF Type 2; C096013:EIF3I protein, human; C012589:trichostatin A; D007335:Insulin-Like Growth Factor II; D012260:Ribonucleases