Growth induction of rat primary hepatocytes using antisense oligonucleotides.
We examined growth control of adult and fetal hepatocytes by regulating the expression of cell-cycle-related proteins using antisense S-oligonucleotides to tumor suppressors retinoblastoma (RB) protein and p53, and cyclin-dependent kinase (CDK) inhibitors p21 and p27. The protein expression in both adult and fetal hepatocytes was significantly suppressed with the addition of corresponding antisense oligonucleotides at a concentration of 2.5 microM. For the evaluation of growth, 3H-thymidine incorporation and DNA content were measured and the results demonstrated that all the antisense oligonucleotides had growth-promoting effects and the promoting potential was equivalent or slightly greater than that with the addition of hepatocyte growth factor (HGF) (10 ng/ml). The growth-promoting effect of the antisense oligonucleotides was enhanced by HGF in both adult and fetal hepatocyte cultures, and the effects on hepatocyte growth were also observed in a suspension culture.
Hamamoto
R
R
Department of Biotechnology, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya 464-8603, Japan.
Seko
H
H
Kamimura
R
R
Yamada
K
K
Murai
K
K
Kamihira
M
M
Iijima
S
S