Oncogene, 2007-07, Vol.26 (34), p.4969-4978
2007
Details
- Autor(en) / Beteiligte
- Titel
- Epigenetic silencing of HSulf-1 in ovarian cancer:implications in chemoresistance
- Ist Teil von
- Oncogene, 2007-07, Vol.26 (34), p.4969-4978
- Ort / Verlag
- Basingstoke: Nature Publishing
- Erscheinungsjahr
- 2007
- Link zum Volltext
- Quelle
- Nexis
- Beschreibungen/Notizen
- To investigate the mechanism by which HSulf-1 expression is downregulated in ovarian cancer, DNA methylation and histone acetylation of HSulf-1 was analysed in ovarian cancer cell lines and primary tumors. Treatment of OV207 and SKOV3 by 5-aza-2'-deoxycytidine resulted in increased transcription of HSulf-1. Sequence analysis of bisulfite-modified genomic DNA from ovarian cell lines and primary tumors without HSulf-1 expression revealed an increase in the frequency of methylation of 12 CpG sites in exon 1A. Chromatin immunoprecipitation assays showed an increase in histone H3 methylation in cell lines without HSulf-1 expression. To assess the significance of HSulf-1 downregulation in ovarian cancer, OV167 and OV202 cells were transfected with HSulf-1 siRNA. Downregulation of HSulf-1 expression in OV167 and OV202 cells lead to an attenuation of cisplatin-induced cytotoxicity. Moreover, patients with ovarian tumors expressing higher levels of HSulf-1 showed a 90% response rate (27/30) to chemotherapy compared to a response rate of 63% (19/30) in those with weak or moderate levels (P=0.0146, chi(2) test). Collectively, these data indicate that HSulf-1 is epigenetically silenced in ovarian cancer and that epigenetic therapy targeting HSulf-1 might sensitize ovarian tumors to conventional first-line therapies.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/sj.onc.1210300Titel-ID: cdi_proquest_miscellaneous_21330963
- Format
- –
- Schlagworte
- Acetylation, Adult, Aged, Aged, 80 and over, Ageing, cell death, Antineoplastic Agents - toxicity, Apoptosis, Azacitidine - analogs & derivatives, Azacitidine - pharmacology, Biological and medical sciences, Bisulfite, Cancer therapies, Cell Line, Tumor, Cell physiology, Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes, Chemoresistance, Chemotherapy, Chromatin, Chromatin - metabolism, Cisplatin, Cisplatin - toxicity, CpG Islands, Cytotoxicity, Deoxyribonucleic acid, DNA, DNA Methylation, Drug resistance, Drug Resistance, Neoplasm - genetics, Enzyme Inhibitors - pharmacology, Epigenesis, Genetic, Epigenetics, Female, Female genital diseases, Fundamental and applied biological sciences. Psychology, Gene expression, Gene Expression Regulation, Neoplastic, Gene Silencing, Genetic aspects, Genetic regulation, Genetics, Genomic analysis, Gynecology. Andrology. Obstetrics, Health aspects, Histone Deacetylase Inhibitors, Histone H3, Histones, Humans, Immunoprecipitation, Medical sciences, Middle Aged, Molecular and cellular biology, Nucleotide sequence, Ovarian cancer, Ovarian Neoplasms - drug therapy, Ovarian Neoplasms - enzymology, Ovarian Neoplasms - genetics, Physiological aspects, Response rates, Sequence analysis, siRNA, Sulfotransferases - genetics, Sulfotransferases - metabolism, Transcription, Tumor cell lines, Tumors