Growth inhibitory effect of interferon-beta is associated with the induction of cyclin-dependent kinase inhibitor p27Kip1 in a human gastric carcinoma cell line.
The effect of IFN-beta on cell growth and the mechanism of growth modulation was examined in human gastric carcinoma cell lines. IFN-beta inhibited the cell growth of TMK-1 cells, whereas it did not affect the growth of the other three cell lines (MKN-7, -28, and -45). The number of apoptotic cells in IFN-beta-treated TMK-1 cells was 2-fold the number of those in control TMK-1 cells, whereas the induction of apoptosis was not observed in IFN-beta-treated MKN-28 cells. IFN-beta enhanced the expression of cyclin-dependent kinase inhibitor p27Kip1 at mRNA and protein levels. The increased p27Kip1 bound preferentially to CDK6. The phosphorylation level of retinoblastoma protein in TMK-1 cells was reduced by IFN-beta treatment. IFN-beta did not affect the expression of cell cycle regulators in MKN-28 cells. These results suggest that the induction of p27Kip1 by IFN-beta might confer inhibition of cell growth, leading to subsequent apoptosis in TMK-1 cells.
Kuniyasu
H
H
First Department of Pathology, Hiroshima University School of Medicine, Japan.
Yasui
W
W
Kitahara
K
K
Naka
K
K
Yokozaki
H
H
Akama
Y
Y
Hamamoto
T
T
Tahara
H
H
Tahara
E
E
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D051361:Cyclin-Dependent Kinase 6; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000737:chemistry / Q000187:drug effects; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016899:Interferon-beta; D017346:Protein Serine-Threonine Kinases; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases