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Data from The Mechanism of DAB2IP in Chemoresistance of Prostate Cancer Cells
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Data from The Mechanism of DAB2IP in Chemoresistance of Prostate Cancer Cells
Data from The Mechanism of DAB2IP in Chemoresistance of Prostate Cancer Cells
KW
Kaijie Wu
Kaijie Wu
DX
Daxing Xie
Daxing Xie
YZ
Yonglong Zou
Yonglong Zou
TZ
Tingting Zhang
Tingting Zhang
RP
Rey-Chen Pong
Rey-Chen Pong
GX
Guanghua Xiao
Guanghua Xiao
LF
Ladan Fazli
Ladan Fazli
MG
Martin Gleave
Martin Gleave
DH
Dalin He
Dalin He
DB
David A. Boothman
David A. Boothman
JH
Jer-Tsong Hsieh
Jer-Tsong Hsieh
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31 March 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/1078-0432.c.6521589.v1
Abstract
Purpose: The docetaxel-based chemotherapy is the standard of care for castration-resistant prostate cancer (CRPC), inevitably, patients develop resistance and decease. Until now, the mechanism and predictive marker for chemoresistance are poorly understood.Experimental Design: Immortalized normal prostate and cancer cell lines stably manipulated with different DAB2IP expression levels were used and treated with chemotherapeutic drugs commonly used in prostate cancer therapy. Cell proliferation was measured using MTT assay; Western blot, quantitative PCR, and luciferase reporter assays were used to analyze Clusterin gene regulation by DAB2IP. Immunohistochemical analysis was conducted for evaluating DAB2IP, Clusterin and Egr-1 expression in human prostate cancer tissue.Results: DAB2IP Knockdown (KD) cells exhibited resistance to several chemotherapeutic drugs, whereas increased DAB2IP in C4-2 cells restored the drug sensitivity. Parallel, DAB2IP KD cells exhibited higher expression of Clusterin, an antiapoptotic factor, whereas elevated DAB2IP in C4-2 cells decreased Clusterin expression. Functionally, knocking down Clusterin by short-hairpin RNA or antisense oligonucleotide OGX-011 decreased drug resistance, whereas overexpressing Clusterin in C4-2 D2 enhanced drug resistance. Mechanistically, DAB2IP blocked the cross-talk between Wnt/β-catenin and IGF-I signaling, leading to the suppression of Egr-1 that is responsible for Clusterin expression. A similar result was observed in the prostate of DAB2IP knockout animals. In addition, we observed a significantly inverse correlation between DAB2IP and Egr-1 or Clusterin expression from clinical tissue microarray.Conclusions: This study unveils a new regulation of the Egr-1/Clusterin signaling network by DAB2IP. Loss of DAB2IP expression in CRPC cells signifies their chemoresistance. Clusterin is a key target for developing more effective CRPC therapy. Clin Cancer Res; 19(17); 4740–9. ©2013 AACR.
Keywords
MTT ASSAY
PROSTATE
DAB2IP EXPRESSION
FUNCTIONALLY
CLUSTERIN
CHEMORESISTANCE
CRPC
EGR
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Open Access