DNMT1 and HDAC1 gene expression in impaired spermatogenesis and testicular cancer

Abstract

DNA methylation catalyzed by DNA methyltransferases (DNMTs) and histone deacetylation catalyzed by histone deacetylases (HDACs) play an important role for the regulation of gene expression during carcinogenesis and spermatogenesis. We therefore studied the cell-specific expression of DNMT1 and HDAC1 for the first time in human testicular cancer and impaired human spermatogenesis. During normal spermatogenesis, DNMT1 and HDAC1 were colocalized in nuclei of spermatogonia. While HDAC1 was additionally present in nuclei of Sertoli cells, DNMT1 was restricted to germ cells exhibiting a different expression pattern of mRNA (in pachytene spermatocytes and round spermatids) and protein (in round spermatids). Interestingly, in infertile patients revealing round spermatid maturation arrest, round spermatids lack DNMT1 protein, while pachytene spermatocytes became immunopositive for DNMT1. In contrast, no changes in the expression pattern could be observed for HDAC1. This holds true also in testicular tumors, where HDAC1 has been demonstrated in embryonal carcinoma, seminoma and teratoma. Interestingly, DNMT1 was not expressed in seminoma, but upregulated in embryonal carcinoma.

Significance of DNA methyltransferase-1 and histone deacetylase-1 in pancreatic cancer

“…The expression of DNMT1 or HDAC1 at both the mRNA and protein levels increase in several human tumors (22)(23)(24)(25)(26). However, no previous studies, have examined their expression in pancreatic cancer, especially in the precancerous lesions of PanINs and IPMNs.…”

Epigenetic Modifications in Testicular Germ Cell Tumors

“…In non-seminomas (8 embryonal carcinomas and 8 teratomas), both mRNA and protein are detected, with a stronger signal observed in the embryonal carcinomas. Neither mRNA nor protein are detected in seminomas (0/16; Omisanjo et al, 2007). These differential TGCT expression patterns of DNMT1 were also found using RNA microarray analysis and quantitative real-time RT-PCR, showing significantly upregulated transcript levels in embryonal carcinomas, but low levels in seminomas .…”

“…Omisanjo and colleagues examined the expression of DNMT1 mRNA and protein in TGCTs to determine whether DNMT1 is upregulated. In normal human adult testis, DNMT1 mRNA is expressed in spermatogonia, pachytene spermatocytes, and round spermatids, as measured by in situ hybridization; the protein is nuclear in spermatogonia, cytoplasmic in round spermatids, and interestingly, is not detected in pachytene spermatocytes (Omisanjo et al, 2007). In non-seminomas (8 embryonal carcinomas and 8 teratomas), both mRNA and protein are detected, with a stronger signal observed in the embryonal carcinomas.…”

“…HDAC1, as with other members of the HDAC family, induces transcriptional repression (De Ruijter et al, 2003). In normal human adult testis, HDAC1 protein is observed in the nuclei of spermatogonia and Sertoli cells (Omisanjo et al, 2007). In both seminomatous and nonseminomatous TGCTs (embryonal carcinomas and teratomas), HDAC1 is consistently detected.…”

“…HDAC1 and H3K9me3, as well as other histone modifying enzymes and modified tail residues, are present in normal human and mouse Sertoli cells (Omisanjo et al, 2007;Payne and Braun, 2006). Because Sertoli cells must maintain constant physical contact with germ cells at all stages inside each seminiferous tubule, the influence they have upon spermatogenesis is profound.…”