RRC ID |
43297
|
著者 |
Osabe M, Sugatani J, Takemura A, Yamazaki Y, Ikari A, Kitamura N, Negishi M, Miwa M.
|
タイトル |
Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation.
|
ジャーナル |
Biochem Biophys Res Commun
|
Abstract |
Constitutive androstane receptor (CAR) is a transcription factor to regulate the expression of several genes related to drug-metabolism. Here, we demonstrate that CAR protein accumulates during G1 in human SW480 and HepG2 cells. After the G1/S phase transition, CAR protein levels decreased, and CAR was hardly detected in cells by the late M phase. CAR expression in both cell lines was suppressed by RNA interference-mediated suppression of CDK4. Depletion of CAR by RNA interference in both cells and by hepatocyte growth factor treatment in HepG2 cells resulted in decreased MDM2 expression that led to p21 upregulation and repression of HepG2 cell growth. Thus, our results demonstrate that CAR expression is an early G1 event regulated by CDK4 that contributes to MDM2 expression; these findings suggest that CAR may influence the expression of genes involved in not only the metabolism of endogenous and exogenous substances but also in the cell proliferation.
|
巻・号 |
369(4)
|
ページ |
1027-33
|
公開日 |
2008-5-16
|
DOI |
10.1016/j.bbrc.2008.02.140
|
PII |
S0006-291X(08)00405-1
|
PMID |
18331826
|
MeSH |
Cell Line, Tumor
Cell Proliferation* / drug effects
Constitutive Androstane Receptor
Cyclin-Dependent Kinase Inhibitor p16 / genetics
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
Cyclin-Dependent Kinase Inhibitor p21 / genetics
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
G1 Phase / drug effects
G1 Phase / genetics*
Gene Expression
Gene Expression Regulation*
Glucuronosyltransferase / genetics
Glucuronosyltransferase / metabolism
Humans
Proto-Oncogene Proteins c-mdm2 / genetics
Proto-Oncogene Proteins c-mdm2 / metabolism
RNA Interference
Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism*
S Phase
Serine Endopeptidases / pharmacology
Transcription Factors / antagonists & inhibitors
Transcription Factors / genetics
Transcription Factors / metabolism*
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism
Up-Regulation
|
IF |
2.985
|
引用数 |
18
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
Hep G2 |