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Apoptosis, growth arrest and suppression of invasiveness by CRE-decoy oligonucleotide in ovarian cancer cells: Protein kinase A downregulation and cytoplasmic export of CRE-binding proteins

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Abstract

The CRE (cyclic AMP response element)-transcription factor complex plays a critical role in response to hormonal signals for cell proliferation, differentiation, and apoptosis. We have reported previously that the CRE-transcription factor decoy oligonucleotide specifically slows tumor cell proliferation and inhibits CRE- and Ap-1-directed transcription in vivo (Park et al., 1999 [12]). We have investigated the effect of inhibiting CRE-directed transcription on ovarian cancer cell growth. Here, we report that CRE-decoy oligonucleotide treatment results in the inhibition of cell growth and a marked reduction in the expression of the regulatory and catalytic subunits of protein kinase A and the type I and type II protein kinase A holoenzymes. Growth inhibition was accompanied by changes in cell morphology, appearance of apoptotic nuclei, and DNA fragmentation. In addition, MMP-9 (matrix methalloproteinase-9) activity was markedly reduced in CRE-decoy treated cells. Indirect immunofluorescence revealed that CRE-decoy oligonucleotide treatment promoted export of the CRE-binding protein, CREB, from the nucleus to the cytoplasm, while importing the catalytic subunit of protein kinase A from the cytoplasm to the nucleus. The results indicate that the decoy oligonucleotide, by binding specifically to CRE-transcription factors, interferes with CRE-directed transcription in vivo. These results show a critical role for CRE-directed transcription in ovarian cancer cell growth. Thus, the CRE-decoy oligonucleotide may provide a powerful means to combat ovarian cancer.

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Authors and Affiliations

  1. Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD, 20892-1750, USA

    Özge Alper & Yoon S. Cho-Chung

  2. Experimental Oncology Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD, 20892-1750, USA

    Elke S. Bergmann-Leitner & Scott Abrams

Authors
  1. Özge Alper
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  2. Elke S. Bergmann-Leitner
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  3. Scott Abrams
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  4. Yoon S. Cho-Chung
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Correspondence to Yoon S. Cho-Chung.

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Alper, Ö., Bergmann-Leitner, E.S., Abrams, S. et al. Apoptosis, growth arrest and suppression of invasiveness by CRE-decoy oligonucleotide in ovarian cancer cells: Protein kinase A downregulation and cytoplasmic export of CRE-binding proteins. Mol Cell Biochem 218, 55–63 (2001). https://doi.org/10.1023/A:1007205205131

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