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  • Oncogenomics
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Differential expression of DOC-1 in microsatellite-unstable human colorectal cancer

Oncogene volume 22, pages 6304–6310 (2003)Cite this article

Abstract

The precise genetic mechanism of malignant transformation in DNA mismatch repair deficient, microsatellite-unstable colorectal cancer (CRC) has yet to be elucidated. We employed cDNA microarray to identify patterns of gene expression among CRC cell lines and to compare directly lines with and without microsatellite instability. This study was undertaken to test the hypothesis that microsatellite-unstable CRC cell lines demonstrate specific patterns of gene expression that differ significantly from those observed among microsatellite-stable CRC. Multiple differential expression patterns were identified. Genes demonstrating differential expression included deleted-in-oral-cancer-1 (DOC-1), a highly conserved growth suppressor. DOC-1 expression correlated with microsatellite status, with significantly decreased expression in microsatellite-unstable cell lines and constitutive expression in microsatellite-stable cell lines. We also observed alterations in the biologic behavior of p12DOC-1-deficient cell lines, with increased S phase and decreased apoptosis compared to microsatellite-stable (DOC-1+) cell lines. Transfection of p12DOC-1 into SW48, which lacks p12DOC-1 expression, resulted in cell cycle and apoptosis profiles similar to other p12DOC-1+ cell lines. These results support the hypothesis that microsatellite-unstable CRC is characterized by novel patterns of gene expression different from those associated with microsatellite-stable CRC, and demonstrate that p12DOC-1 has tumor suppressor potential in colon epithelial cells.

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Acknowledgements

We thank Dr DT Wong for the p12DOC-1 expression plasmid. We also thank Dr L Augenlicht for the gift of the cell lines used in this study, and for his critical review of the manuscript.

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Authors and Affiliations

  1. Department of Molecular Genetics, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Ullmann 1219, Bronx, 10461, NY, USA

    Ziqiang Yuan

  2. Department of Surgery, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Ullmann 1219, Bronx, 10461, NY, USA

    Tara Sotsky Kent

  3. Department of Surgery and Molecular Genetics, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Ullmann 1219, Bronx, 10461, NY, USA

    Thomas K Weber

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  1. Ziqiang Yuan
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  2. Tara Sotsky Kent
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Correspondence to Thomas K Weber.

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This work was supported in part by an AECOM Cancer Center support grant to Thomas K Weber.

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Yuan, Z., Sotsky Kent, T. & Weber, T. Differential expression of DOC-1 in microsatellite-unstable human colorectal cancer. Oncogene 22, 6304–6310 (2003). https://doi.org/10.1038/sj.onc.1206609

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