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