Fibroblast-like transformation and c-myc gene alteration of human hepatocytes induced by novobiocin and butyrate.
Topoisomerase II inhibitor novobiocin and deacetylase inhibitor sodium butyrate synergistically transformed Chang liver cells into fibroblast-like cells. In these fibroblast-like cells, the production of type III procollagen was increased and the DNase I hypersensitivity of c-myc gene was reduced. In addition, these changes were associated with an increased acetylation of nuclear proteins, especially those of DNase I sensitive nucleosomes. Therefore, it is suggested that chemical modulation of nuclear proteins by novobiocin and butyrate may be responsible, at least partly, for the alteration of the chromatin structure of c-myc gene and the fibroblast-like transformation of Chang liver cells.
Kaneko
Y
Y
First Department of Medicine, University of Tokyo, Japan.
Nakayama
T
T
Hamasaki
T
T
Tsukamoto
A
A
Toda
G
G
Oka
H
H
D002087:Butyrates; D020148:Butyric Acid; D002461:Cell Line, Transformed; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D003850:Deoxyribonuclease I; D004357:Drug Synergism; D004847:Epithelial Cells; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology*; D009675:Novobiocin; D009857:Oncogenes / Q000187:drug effects
D002087:Butyrates; D020148:Butyric Acid; D009675:Novobiocin; D003850:Deoxyribonuclease I; D004250:DNA Topoisomerases, Type II