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CUGBP2 Plays a Critical Role in Apoptosis of Breast Cancer Cells in Response to Genotoxic Injury
Author(s) -
MUKHOPADHYAY DEBNATH,
JUNG JESSE,
MURMU NABENDU,
HOUCHEN COURTNEY W.,
DIECKGRAEFE BRIAN K.,
ANANT SHRIKANT
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1299.093
Subject(s) - apoptosis , messenger rna , small interfering rna , gene silencing , downregulation and upregulation , gene expression , cancer research , cancer cell , microbiology and biotechnology , biology , chemistry , cancer , rna , gene , biochemistry , genetics
A bstract : Posttranscriptional control of gene expression plays a key role in regulating gene expression in cells undergoing apoptosis. Cyclooxygenase‐2 (COX‐2) is a crucial enzyme in the conversion of arachidonic acid to prostaglandin E2 (PGE 2 ) and is significantly upregulated in many types of adenocarcinomas. COX‐2 overexpression leads to increased PGE 2 production, resulting in increased cellular proliferation. PGE 2 enhances the resistance of cells to ionizing radiation. Accordingly, understanding mechanisms regulating COX‐2 expression may lead to important therapeutic advances. Besides transcriptional control, COX‐2 expression is significantly regulated by mRNA stability and translation. We have previously demonstrated that RNA binding protein CUGBP2 binds AU‐rich sequences to regulate COX‐2 mRNA translation. In the current study, we have determined that expression of both COX‐2 mRNA and CUGBP2 mRNA are induced in MCF‐7 cells, a breast cancer cell line, following exposure to 12 Gy γ‐irradiation. However, only CUGBP2 protein is induced, but COX‐2 protein levels were not altered. Silencer RNA (siRNA)‐mediated inhibition of CUGBP2 reversed the block in COX‐2 protein expression. Furthermore, MCF‐7 cells underwent apoptosis in response to radiation injury, which was also reversed by CUGBP2 siRNAs. These data suggest that CUGBP2 is a critical regulator of the apoptotic response to genotoxic injury in breast cancer cells.