Aberrant promoter methylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma

M. S. Kim, X. Chang, K. Yamashita, J. K. Nagpal, J. H. Baek, G. Wu, B. Trink, E. A. Ratovitski, Masaki Mori, D. Sidransky

Research output: Contribution to journalArticle

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Abstract

To identify novel methylated gene promoters, we compared differential RNA expression profiles of colorectal cancer (CRC) cell lines with or without treatment of 5-aza-2′-deoxycytidine (5-aza-dC). Out of 1776 genes that were initially 'absent (that is, silenced)' by gene expression array analysis, we selected 163 genes that were increased after 5-aza-dC treatment in at least two of three CRC cell lines. The microarray results were confirmed by Reverse Transcription-PCR, and CpG island of the gene promoters were amplified and sequenced for examination of cancer-specific methylation. Among the genes identified, the deafness, autosomal dominant 5 gene, DFNA5, promoter was found to be methylated in primary tumor tissues with high frequency (65%, 65/100). Quantitative methylation-specific PCR of DFNA5 clearly discriminated primary CRC tissues from normal colon tissues (3%, 3/100). The mRNA expression of DFNA5 in four of five colon cancer tissues was significantly downregulated as compared to normal tissues. Moreover, forced expression of full-length DFNA5 in CRC cell lines markedly decreased the cell growth and colony-forming ability whereas knockdown of DFNA5 increased cell growth in culture. Our data implicate DFNA5 as a novel tumor suppressor gene in CRC and a valuable molecular marker for human cancer.

Original languageEnglish
Pages (from-to)3624-3634
Number of pages11
JournalOncogene
Volume27
Issue number25
DOIs
Publication statusPublished - Jun 5 2008

Fingerprint

Carcinogens
Methylation
Colorectal Neoplasms
decitabine
Genes
Cell Line
Dominant Genes
Neoplasms
Polymerase Chain Reaction
CpG Islands
Deafness
Growth
Tumor Suppressor Genes
Colonic Neoplasms
Reverse Transcription
Autosomal Dominant 5 Deafness
Colon
Down-Regulation
RNA
Gene Expression

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Kim, M. S., Chang, X., Yamashita, K., Nagpal, J. K., Baek, J. H., Wu, G., ... Sidransky, D. (2008). Aberrant promoter methylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma. Oncogene, 27(25), 3624-3634. https://doi.org/10.1038/sj.onc.1211021

Aberrant promoter methylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma. / Kim, M. S.; Chang, X.; Yamashita, K.; Nagpal, J. K.; Baek, J. H.; Wu, G.; Trink, B.; Ratovitski, E. A.; Mori, Masaki; Sidransky, D.

In: Oncogene, Vol. 27, No. 25, 05.06.2008, p. 3624-3634.

Research output: Contribution to journalArticle

Kim, MS, Chang, X, Yamashita, K, Nagpal, JK, Baek, JH, Wu, G, Trink, B, Ratovitski, EA, Mori, M & Sidransky, D 2008, 'Aberrant promoter methylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma', Oncogene, vol. 27, no. 25, pp. 3624-3634. https://doi.org/10.1038/sj.onc.1211021
Kim, M. S. ; Chang, X. ; Yamashita, K. ; Nagpal, J. K. ; Baek, J. H. ; Wu, G. ; Trink, B. ; Ratovitski, E. A. ; Mori, Masaki ; Sidransky, D. / Aberrant promoter methylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma. In: Oncogene. 2008 ; Vol. 27, No. 25. pp. 3624-3634.
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