cytidylyl-3--5--guanosine and Precancerous-Conditions
cytidylyl-3--5--guanosine has been researched along with Precancerous-Conditions* in 2 studies
Other Studies
2 other study(ies) available for cytidylyl-3--5--guanosine and Precancerous-Conditions
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Dynamic regulation of estrogen receptor-beta expression by DNA methylation during prostate cancer development and metastasis.
Estrogen receptor (ER)-beta is thought to exert anti-proliferative effects in the normal prostate but supports prostate cancer (PCa) cell survival. We previously reported that the receptor's expression declined as PCa developed in the gland but reappeared in lymph node and bone metastases. To investigate whether hypermethylation was the underlying mechanism for these phenomena, we first identified two CpG islands (CGIs) encompassing 41 CpG dinucleotides, located separately in the untranslated exon 0N and the promoter region of ER-beta. Using immunostained, laser capture-microdissected samples from 56 clinical specimens, we demonstrated an inverse relationship exists between the extent of ER-beta CGI methylation and receptor expression in normal, hyperplastic, premalignant, and malignant foci of the prostate and in lymph node and bone metastases. Treatment of PCa cell lines (LNCaP and DU145), that express little ER-beta mRNA, with a demethylating agent increased levels of receptor expression thus corroborating our in vivo findings that methylation is involved in ER-beta silencing. Methylation centers in the promoter region and exon 0N were identified by hierarchical cluster analysis of bisulfite sequencing data obtained from 710 alleles. Methylation at these centers was insignificant in normal epithelium, reached 80 to 90% in grade 4/5 PCa, but declined to less than 20% in bone metastases. In addition, progressive methylation spreading from the exonic CGI to the promoter CGI, which correlated with loss of ER-beta expression, was detected in microdissected samples and in cell cultures. Using a new class of methylated oligonucleotides that mediate sequence-specific methylation in cellulo, we demonstrated that methylation of the promoter CGI, but not the exonic CGIs, led to transcriptional inactivation of ER-beta. Our results present the first evidence that epigenetic regulation of ER-beta is a reversible and tumor stage-specific process and that gene silencing via methylated oligonucleotides may have therapeutic potential in the treatment of advanced PCa. Topics: Base Sequence; Cell Line, Tumor; Dinucleoside Phosphates; DNA Methylation; DNA Primers; Estrogen Receptor beta; Humans; Male; Molecular Sequence Data; Neoplasm Metastasis; Neoplasm Staging; Precancerous Conditions; Promoter Regions, Genetic; Prostatic Neoplasms; Receptors, Estrogen; TATA Box | 2004 |
The E-cadherin gene is silenced by CpG methylation in human hepatocellular carcinomas.
Our study was designed to clarify the significance of silencing the E-cadherin gene, which is located on 16q22.1, due to CpG methylation during hepatocarcinogenesis. The CpG methylation status of primary hepatocellular carcinomas (HCCs) and corresponding liver tissues showing chronic hepatitis or cirrhosis, which are widely considered to be precancerous conditions, were assessed by digesting DNA with methylation-sensitive and non-sensitive restriction enzymes. CpG methylation around the promoter region of the E-cadherin gene was detected in 46% of liver tissues showing chronic hepatitis or cirrhosis and 67% of HCCs examined. Immunohistochemical examination revealed reduced E-cadherin expression in 59% of HCCs examined. CpG methylation around the promoter region correlated significantly with reduced E-cadherin expression in HCCs (p < 0.05). CpG methylation around the promoter region, which increases during the progression from a precancerous condition to HCC, may participate in hepatocarcinogenesis through reduction of E-cadherin expression, resulting in loss of intercellular adhesiveness and destruction of tissue morphology. Topics: Cadherins; Carcinoma, Hepatocellular; Dinucleoside Phosphates; DNA Methylation; DNA Restriction Enzymes; DNA, Neoplasm; Humans; Immunohistochemistry; Liver; Liver Neoplasms; Precancerous Conditions; Promoter Regions, Genetic | 1997 |