The loss of NKX3.1 expression in testicular – and prostate – cancers is not caused by promoter hypermethylation

• Main Authors: Esteller Manel, Saatcioglu Fahri, Henrique Rui, Abeler Vera M, Fraga Mario F, Skotheim Rolf I, Lind Guro E, Teixeira Manuel R, Lothe Ragnhild A
• Format: Article
• Language: English
• Published: BMC 2005-02-01
• Series: Molecular Cancer
• Online Access: http://www.molecular-cancer.com/content/4/1/8

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated that the NKX3.1 protein is commonly down-regulated in testicular germ cell tumors (TGCTs) and prostate carcinomas. The homeobox gene <it>NKX3.1 </it>maps to chromosome band 8p21, which is a region frequently lost in prostate cancer, but not in TGCT. Mutations have not been reported in the <it>NKX3.1 </it>sequence, and the gene is hypothesized to be epigenetically inactivated. In the present study we examined the methylation status of the <it>NKX3.1 </it>promoter in relevant primary tumors and cell lines: primary TGCTs (n = 55), intratubular germ cell neoplasias (n = 7), germ cell tumor cell lines (n = 3), primary prostate adenocarcinomas (n = 20), and prostate cancer cell lines (n = 3) by methylation-specific PCR and bisulphite sequencing.</p> <p>Results and Conclusions</p> <p>Down-regulation of NKX3.1 expression was generally not caused by promoter hypermethylation, which was only found in one TGCT. However, other epigenetic mechanisms, such as modulation of chromatin structure or modifications of histones, may explain the lack of NKX3.1 expression, which is seen in most TGCTs and prostate cancer specimens.</p>