Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation
| Autor: | Akiko Takemura, Masahiko Negishi, Akira Ikari, Naomi Kitamura, Junko Sugatani, Makoto Osabe, Masao Miwa, Yasuhiro Yamazaki |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Biophysics Gene Expression Receptors Cytoplasmic and Nuclear Biology Biochemistry S Phase Downregulation and upregulation RNA interference Cell Line Tumor Constitutive androstane receptor medicine Humans Glucuronosyltransferase Molecular Biology Transcription factor Constitutive Androstane Receptor Cyclin-Dependent Kinase Inhibitor p16 Cell Proliferation Cell growth Serine Endopeptidases G1 Phase RNA Proto-Oncogene Proteins c-mdm2 Cell Biology Molecular biology Up-Regulation Cell biology Gene Expression Regulation Cell culture RNA Interference Hepatocyte growth factor Tumor Suppressor Protein p53 human activities Transcription Factors medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 369:1027-1033 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2008.02.140 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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