Interferon modulates the messenger RNA of G1-controlling genes to suppress the G1-to-S transition in Daudi cells.
Interferon (IFN) is one of the potent antiproliferative cytokines and is used to treat some selected cancers. IFN arrests the growth of Burkitt Lymphoma derived cell line Daudi cells in the G1 phase. G1-to-S progression is controlled by positive and negative regulatory genes. Therefore, we investigated the effects of IFN on G1-controlling genes. Expression of cyclin-dependent kinases (Cdks 2, 3, 4, 5, 6), MO15/Cdk7, and cyclins E and H was studied to assess positive regulators, while p15Ink4B, p16Ink4, p18, p21Cip1, and p27Kip1 were assessed as negative regulators. Cdks 2, 4, 6 and cyclin E were markedly down-regulated. MO15/Cdk7 expression showed little change, but its regulatory subunit (cyclin H) was down-regulated like cyclin E. Expression of p15Ink4B and p16Ink4 was not observed. p18 was induced until 48 h and its expression returned to the initial level at 72 h. In contrast, p21Cip1 mRNA expression remained at the baseline level throughout IFN treatment, while the expression of p27Kip1 increased at 48 and 72 h. Taken together, these data indicate that IFN changes the messenger RNA of G1-controlling genes towards the suppression of G1-to-S transition.
Yamada
H
H
Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Ochi
K
K
Nakada
S
S
Takahara
S
S
Nemoto
T
T
Sekikawa
T
T
Horiguchi-Yamada
J
J
D001483:Base Sequence; D015152:Blotting, Northern; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D016193:G1 Phase / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D016898:Interferon-alpha / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D016196:S Phase / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D012333:RNA, Messenger