CUGBP2 Plays a Critical Role in Apoptosis of Breast Cancer Cells in Response to Genotoxic Injury

Debnath Mukhopadhyay, Jesse Jung, Nabendu Murmu, Courtney W. Houchen, Brian K. Dieckgraefe, Shrikant Anant

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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 (PGE2) 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.

Original languageEnglish
Pages (from-to)504-509
Number of pages6
JournalAnnals of the New York Academy of Sciences
Volume1010
DOIs
StatePublished - Jan 1 2003

Keywords

  • AU-rich sequence
  • Cyclooxygenase-2
  • RNA binding proteins
  • Radiation-induced injury

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