Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation

Osabe, Makoto; Sugatani, Junko; Takemura, Akiko; Yamazaki, Yasuhiro; Ikari, Akira; Kitamura, Naomi; Negishi, Masahiko; Miwa, Masao

doi:10.1016/j.bbrc.2008.02.140

Title: Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation

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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.

Authors:

Osabe, Makoto ^[1]; Sugatani, Junko ^[1]; Takemura, Akiko; Yamazaki, Yasuhiro; Ikari, Akira ^[1]; Kitamura, Naomi ^[2]; Negishi, Masahiko ^[3]; Miwa, Masao ^[1]

Department of Pharmaco-Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan)
Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama (Japan)
Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (United States)

Publication Date:: Fri May 16 00:00:00 EDT 2008

OSTI Identifier:: 21143678

Resource Type:: Journal Article

Journal Name:: Biochemical and Biophysical Research Communications

Additional Journal Information:: Journal Volume: 369; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2008.02.140; PII: S0006-291X(08)00405-1; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; DRUGS; GENES; GROWTH FACTORS; METABOLISM; MONOCLINIC LATTICES; PHASE TRANSFORMATIONS; RECEPTORS; RNA; TRANSCRIPTION FACTORS

Citation Formats


                    Osabe, Makoto, Sugatani, Junko, Global COE Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Takemura, Akiko, Yamazaki, Yasuhiro, Ikari, Akira, Kitamura, Naomi, Negishi, Masahiko, and Miwa, Masao. Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation.  United States: N. p., 2008. 
        Web.  doi:10.1016/j.bbrc.2008.02.140.

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                    Osabe, Makoto, Sugatani, Junko, Global COE Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Takemura, Akiko, Yamazaki, Yasuhiro, Ikari, Akira, Kitamura, Naomi, Negishi, Masahiko, & Miwa, Masao. Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation.  United States.  https://doi.org/10.1016/j.bbrc.2008.02.140

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                    Osabe, Makoto, Sugatani, Junko, Global COE Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Takemura, Akiko, Yamazaki, Yasuhiro, Ikari, Akira, Kitamura, Naomi, Negishi, Masahiko, and Miwa, Masao. 2008.  
        "Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation".  United States.  https://doi.org/10.1016/j.bbrc.2008.02.140.

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@article{osti_21143678,

  title        = {Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation},

  author       = {Osabe, Makoto and Sugatani, Junko and Global COE Program, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka and Takemura, Akiko and Yamazaki, Yasuhiro and Ikari, Akira and Kitamura, Naomi and Negishi, Masahiko and Miwa, Masao},

  abstractNote = {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.},

  doi          = {10.1016/j.bbrc.2008.02.140},

  url          = {https://www.osti.gov/biblio/21143678},
  journal      = {Biochemical and Biophysical Research Communications},

  issn         = {0006-291X},

  number       = 4,

  volume       = 369,

  place        = {United States},

  year         = {Fri May 16 00:00:00 EDT 2008},

  month        = {Fri May 16 00:00:00 EDT 2008}

}

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