TY - JOUR
T1 - Identification of Aryl Hydrocarbon Receptor as a Putative Wnt/β-Catenin Pathway Target Gene in Prostate Cancer Cells
AU - Chesire, Dennis R.
AU - Dunn, Thomas A.
AU - Ewing, Charles M.
AU - Luo, Jun
AU - Isaacs, William B.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/4/1
Y1 - 2004/4/1
N2 - Recent genetic and functional analyses have implicated the wnt/β-catenin signaling pathway in prostate cancer (CaP) pathogenesis. Thus, there is much interest in understanding the consequences of wnt signaling in CaP; target gene expression is one important area of inquiry and is the focus of this report. Adenoviral-mediated overexpression of a mutant, hyperactive form of β-catenin in CWR22-Rv1 CaP cells led to increased aryl hydrocarbon receptor (AhR, or dioxin receptor) and transmembrane protein 2 RNA transcript expression, as detected by cDNA-microarray analyses. Validating these results, reverse transcription-PCR assays demonstrated that in CWR22-Rv1 cells as well as in LAPC-4 CaP cells, increased putative target gene RNA expression occurs with transient overexpression of mutant β-catenin, treatment of cells with lithium chloride, or with wnt3a-conditioned medium, three distinct modes of experimental wnt/β-catenin pathway activation. This β-catenin-associated expression of AhR and transmembrane protein 2 does not require de novo protein synthesis and may only involve a certain subset of CaP cell lines. Western and immunofluorescence analyses were undertaken to assess the relationship between the wnt/β-catenin-stimulated increase in AhR transcripts and AhR protein expression; we provide evidence that an association exists whereby up-regulation of AhR RNA by wnt or β-catenin is coupled with augmented AhR protein levels. Intriguingly, these studies also demonstrated that nuclear β-catenin staining may not be a sole deciding factor when predicting the status of wnt/β-catenin signaling in CaP cells. Finally, the extent to which wnt signaling may synergize with an environmental agonist of AhR (2,3,7,8-tetrachlorodibenzo-p-dioxin) to potentiate AhR transcriptional activity was examined. Considering previous work linking AhR to processes of development and carcinogenesis, our data may highlight one particular role for wnt/β-catenin signaling in prostate tumor biology.
AB - Recent genetic and functional analyses have implicated the wnt/β-catenin signaling pathway in prostate cancer (CaP) pathogenesis. Thus, there is much interest in understanding the consequences of wnt signaling in CaP; target gene expression is one important area of inquiry and is the focus of this report. Adenoviral-mediated overexpression of a mutant, hyperactive form of β-catenin in CWR22-Rv1 CaP cells led to increased aryl hydrocarbon receptor (AhR, or dioxin receptor) and transmembrane protein 2 RNA transcript expression, as detected by cDNA-microarray analyses. Validating these results, reverse transcription-PCR assays demonstrated that in CWR22-Rv1 cells as well as in LAPC-4 CaP cells, increased putative target gene RNA expression occurs with transient overexpression of mutant β-catenin, treatment of cells with lithium chloride, or with wnt3a-conditioned medium, three distinct modes of experimental wnt/β-catenin pathway activation. This β-catenin-associated expression of AhR and transmembrane protein 2 does not require de novo protein synthesis and may only involve a certain subset of CaP cell lines. Western and immunofluorescence analyses were undertaken to assess the relationship between the wnt/β-catenin-stimulated increase in AhR transcripts and AhR protein expression; we provide evidence that an association exists whereby up-regulation of AhR RNA by wnt or β-catenin is coupled with augmented AhR protein levels. Intriguingly, these studies also demonstrated that nuclear β-catenin staining may not be a sole deciding factor when predicting the status of wnt/β-catenin signaling in CaP cells. Finally, the extent to which wnt signaling may synergize with an environmental agonist of AhR (2,3,7,8-tetrachlorodibenzo-p-dioxin) to potentiate AhR transcriptional activity was examined. Considering previous work linking AhR to processes of development and carcinogenesis, our data may highlight one particular role for wnt/β-catenin signaling in prostate tumor biology.
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U2 - 10.1158/0008-5472.CAN-03-3309
DO - 10.1158/0008-5472.CAN-03-3309
M3 - Article
C2 - 15059908
AN - SCOPUS:1942538298
SN - 0008-5472
VL - 64
SP - 2523
EP - 2533
JO - Cancer Research
JF - Cancer Research
IS - 7
ER -