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Cancers 2011, 3(4), 3714-3725;

DNA Methylation and the HOXC6 Paradox in Prostate Cancer

Department of Urology, Heinrich Heine University, Moorenstr. 5, 40225 Düsseldorf, Germany
Author to whom correspondence should be addressed.
Received: 4 August 2011 / Revised: 8 September 2011 / Accepted: 22 September 2011 / Published: 27 September 2011
(This article belongs to the Special Issue Prostate Cancer)
Full-Text   |   PDF [258 KB, uploaded 27 September 2011]


Overexpression of the classical homeobox transcription factor HOXC6 is frequent in prostate cancers and correlates with adverse clinical parameters. Since surprisingly many HOXC6 target genes are downregulated in prostate cancer, it has been posited that oncogenic effects of HOXC6 in prostate cancer may be unmasked by concurrent epigenetic downregulation of target genes exerting tumor suppressive effects. To test this hypothesis, we have studied the expression of three HOXC6 target genes, CNTN1 (encoding a cell adhesion protein), DKK3 and WIF1 (encoding WNT growth factor antagonists) as well as DNA methylation of DKK3 and WIF1. HOXC6 upregulation and association with poor prognosis were confirmed in our tissue series. The three target genes were each significantly downregulated in cancer tissues and expression of each one correlated inversely with that of HOXC6. Cases with lower WIF1 expression showed significantly earlier recurrence (p = 0.021), whereas no statistical significance was reached for CNTN1 and DKK3. Hypermethylation of DKK3 or WIF1 gene promoters was observed in a subset of cancers with downregulated expression, but was often weak. Our data support the hypothesis that HOXC6 target genes exerting tumor-suppressive effects are epigenetically downregulated in prostate cancer, but DNA methylation appears to follow or bolster rather than to cause their transcriptional inactivation. View Full-Text
Keywords: prostate cancer; epigenetic silencing; DNA methylation; homeobox transcription factors; WNT signaling prostate cancer; epigenetic silencing; DNA methylation; homeobox transcription factors; WNT signaling
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Vinarskaja, A.; Yamanaka, M.; Ingenwerth, M.; Schulz, W.A. DNA Methylation and the HOXC6 Paradox in Prostate Cancer. Cancers 2011, 3, 3714-3725.

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