N-Myc Downstream-Regulated Gene 4 (NDRG4): A Candidate Tumor Suppressor Gene and Potential Biomarker for Colorectal Cancer

Veerle Melotte, Marjolein H F M Lentjes, Sandra M. Van Den Bosch, Debby M E I Hellebrekers, Joep P J De Hoon, Kim A D Wouters, Kathleen L J Daenen, Iris E J M Partouns-Hendriks, Filip Stessels, Joost Louwagie, Kim M. Smits, Matty P. Weijenberg, Silvia Sanduleanu, Carolina A J Khalid-De Bakker, Frank A. Oort, Gerrit A. Meijer, Daisy M A E Jonkers, James G. Herman, Adriaan P. De Bruïne, Manon Van Engeland

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Abstract

BackgroundIdentification of hypermethylated tumor suppressor genes in body fluids is an appealing strategy for the noninvasive detection of colorectal cancer. Here we examined the role of N-Myc downstream-regulated gene 4 (NDRG4) as a novel tumor suppressor and biomarker in colorectal cancer.MethodsNDRG4 promoter methylation was analyzed in human colorectal cancer cell lines, colorectal tissue, and noncancerous colon mucosa by using methylation-specific polymerase chain reaction (PCR) and bisulfite sequencing. NDRG4 mRNA and protein expression were studied using real-time-PCR and immunohistochemistry, respectively. Tumor suppressor functions of NDRG4 were examined by colony formation, cell proliferation, and migration and invasion assays in colorectal cancer cell lines that were stably transfected with an NDRG4 expression construct. Quantitative methylation-specific PCR was used to examine the utility of NDRG4 promoter methylation as a biomarker in fecal DNA from 75 colorectal cancer patients and 75 control subjects. All P values are two-sided.ResultsThe prevalence of NDRG4 promoter methylation in two independent series of colorectal cancers was 86% (71/83) and 70% (128/184) compared with 4% (2/48) in noncancerous colon mucosa (P

Original languageEnglish (US)
Pages (from-to)916-927
Number of pages12
JournalJournal of the National Cancer Institute
Volume101
Issue number13
DOIs
StatePublished - Jul 2009

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Melotte, V., Lentjes, M. H. F. M., Van Den Bosch, S. M., Hellebrekers, D. M. E. I., De Hoon, J. P. J., Wouters, K. A. D., Daenen, K. L. J., Partouns-Hendriks, I. E. J. M., Stessels, F., Louwagie, J., Smits, K. M., Weijenberg, M. P., Sanduleanu, S., Khalid-De Bakker, C. A. J., Oort, F. A., Meijer, G. A., Jonkers, D. M. A. E., Herman, J. G., De Bruïne, A. P., & Van Engeland, M. (2009). N-Myc Downstream-Regulated Gene 4 (NDRG4): A Candidate Tumor Suppressor Gene and Potential Biomarker for Colorectal Cancer. Journal of the National Cancer Institute, 101(13), 916-927. https://doi.org/10.1093/jnci/djp131