2010-01-21Zeitschriftenartikel DOI: 10.1002/gcc.20751
Regulation of human endogenous retrovirus-K expression in melanomas by CpG methylation
The overall prognosis of patients with advanced melanoma is poor due to the lack of effective treatment. A key factor for successful therapy is an early detection of disease. Therefore, reliably detection methods and meaningful tumor markers are required. Expression of the human endogenous retrovirus (HERV)-K(HML-2) was found elevated in melanomas and it was shown that HERV-K supports the in vitro transition of melanoma cells from adherent to a more malignant, nonadherent phenotype. Furthermore, the detection of HERV-K-specific antibodies in melanoma patients was found to correlate with reduced survival. However, the reason for HERV-K expression in melanomas still remains unclear and its use as a tumor marker needs further investigation. Therefore, the tumor-specific transcriptional regulation of HERV-K expression in melanoma was studied in detail. Human melanoma cell lines were investigated for HERV-K expression using real-time PCR. Five cell lines showed very high levels of HERV-K mRNA as a result of increased promoter activity. This promoter activity was directly silenced by DNA methylation in reporter gene experiments. Higher levels of long terminal repeat (LTR) methylation in cells not expressing HERV-K compared with cells expressing HERV-K were found using methylation-sensitive PCR and bisulfite sequencing. Treatment of cell lines with the demethylating agent 5-aza-2′-deoxycytidine resulted in increased levels of HERV-K expression in cells previously not expressing HERV-K and it was shown that this increase is not the result of transcription factor activation. These results demonstrate that increased HERV-K expression in melanomas may be due to increased promoter activity and demethylation of the 5′LTR.
No license information
Show related Items with similar Title, Author, Creator or Subject.
2007-05-25ZeitschriftenartikelFepA- and TonB-dependent bacteriophage H8: receptor binding and genomic sequence. Rabsch, Wolfgang; Ma, Li; Wiley, Graham; Najar, Fares Z.; Kaserer, Wallace; Schuerch, Daniel W.; Klebba, Joseph E.; Roe, Bruce A.; Gomez, Jenny A. Laverde; Schallmey, Marcus; Newton, Salete M. C.; Klebba, Phillip E.H8 is derived from a collection of Salmonella enterica serotype Enteritidis bacteriophage. Its morphology and genomic structure closely resemble those of bacteriophage T5 in the family Siphoviridae. H8 infected S. enterica ...
2005-06-20ZeitschriftenartikelViral promoters can initiate expression of toxin genes introduced into Escherichia coli Lewin, Astrid; Mayer, Martin; Chusainow, Janet; Jacob, Daniela; Appel, BerndBackground: The expression of recombinant proteins in eukaryotic cells requires the fusion of the coding region to a promoter functional in the eukaryotic cell line. Viral promoters are very often used for this purpose. ...
2013-08-08ZeitschriftenartikelCytomegalovirus Downregulates IRE1 to Repress the Unfolded Protein Response Stahl, Sebastian; Burkhart, Julia M.; Hinte, Florian; Tirosh, Boaz; Mohr, Hermine; Zahedi, René P.; Sickmann, Albert; Ruzsics, Zsolt; Budt, Matthias; Brune, WolframDuring viral infection, a massive demand for viral glycoproteins can overwhelm the capacity of the protein folding and quality control machinery, leading to an accumulation of unfolded proteins in the endoplasmic reticulum ...