title: Epigenetic silencing of endothelin-3 in colorectal cancer.
abstract: Endothelins are expressed in a variety of human tissue and are involved in the processes as proliferation, migration and differentiation. The signal transduction pathway is a result of the endothelin-1-3 (ET1-3) binding to their receptors (ETAR, ETBR). ET-3 is a new candidate tumour suppressor gene, which is often downregulated or silenced in human cancer.The aim of the study was to examine DNA methylation of ET-3 genes in colorectal cancer (CRC) tissue samples in relation to the clinical stage (CS) of cancer. The paper is a continuation of our previously published results, which showed a four-fold transcriptional silencing of the ET-3 gene in the samples of colorectal cancer in comparison to normal tissues.A total of 66 paired CRC and normal (surgical margin) tissue samples were used in the study. The tumour tissues were collected from CRC patients in CS I-IV according the 7th edition of UICC TNM Classification of Malignant Tumours (CS I, n = 8; CS II, n = 20; CS III, n = 27; CS IV, n = 11). Assessment of epigenetic silencing of the ET-3 encoding gene was performed in three steps. The silencing of the ET-3 encoding gene was a result from methylation of the promoter sequence using methylation-specific PCR (MS-PCR). Analyses were performed using primers complementary for a CpG island in the first exon of the gene encoding ET-3. An epigenetic silence through methylation of 7.5% (5/66) in comparison to control was observed, including 10% of CS II (2/20), 7% of CS III (2/27) and 9% of CS IV (1/11). The controls and the samples of tumour in CS I showed no epigenetic silencing via methylation. In conclusion, epigenetic silencing of ET-3 in CRC could play a role in the progression than in the induction process. EDN3 would be a future target for epigenetic therapy in colorectal cancer, but further clinical studies are needed.
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Department of Molecular Biology, Sosnowiec, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Olender
authors.affiliation: School of Public Health, Medical University of Silesia, Department of Internal Diseases, Bytom, Poland ewanz@onet.eu.
authors.forename: E
authors.initials: E
authors.lastname: Nowakowska-Zajdel
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Department of Molecular Biology, Sosnowiec, Poland.
authors.forename: C
authors.initials: C
authors.lastname: Kruszniewska-Rajs
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Department of Molecular Biology, Sosnowiec, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Orchel
authors.affiliation: School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Department of Molecular Biology, Sosnowiec, Poland.
authors.forename: U
authors.initials: U
authors.lastname: Mazurek
authors.affiliation: Faculty of Energy and Environmental Engineering, Silesian University of Technology, Gliwice, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Wierzgoń
authors.affiliation: School of Public Health, Medical University of Silesia, Department of Internal Diseases, Bytom, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Kokot
authors.affiliation: School of Public Health, Medical University of Silesia, Department of Internal Diseases, Bytom, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Muc-Wierzgoń
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D019332:Endothelin-1 / Q000235:genetics; D019334:Endothelin-3 / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D019332:Endothelin-1; D019334:Endothelin-3
keywords: colorectal cancer; endothelin-3; epigenetic silencing; tissue samples