title: Promoter Hypermethylation and Decreased Expression of Syncytin-1 in Pancreatic Adenocarcinomas.
abstract: Syncytin-1 is a member of human endogenous retroviral W gene family (HERVW1). Known to be expressed in human placental trophoblast, syncytin-1 protein mediates the fusion of cytotrophoblasts for the formation of syncytiotrophoblasts, the terminally differentiated form of trophoblast lineage. In addition, in vitro studies indicate that syncytin-1 possessed nonfusogenic functions such as those for immune suppression, cell cycle regulation and anti-apoptotic activities. Overexpression of syncytin-1 has been observed in various malignant tissues including breast, endometrial and ovarian cancers. It was reported that syncytin-1 gene expression is associated with dynamic changes of DNA hypomethylation in the 5' LTR. In this study, applying the real-time PCR, Western blot analysis and immunohistochemistry methods, we demonstrate a constitutive expression of syncytin-1 in normal pancreas tissues as well as normal tissues adjacent to cancer lesions. Moreover, a reduced expression is found in the pancreatic adenocarcinoma tissues. The expression levels of syncytin-1 are not correlated with the stage, historical grade and gender, but inversely correlated with patients' age. Furthermore, COBRA and bisulfite sequencing results indicated that the lower expression of syncytin-1 is correlated with the hypermethylation of two CpG dinucleotides in the 5' LTR of syncytin-1 gene. The nonfusogenic function of syncytin-1 in normal pancreas as well as its role(s) in the pathogenesis and progression of pancreatic cancers remains to be investigated. Identification of the two CpG dinucleotides around transcription start site as key epigenetic elements has provided valuable information for further studies on the epigenetic regulation of syncytin-1 in pancreatic cancer cells.
authors.affiliation: Department of Histology and Embryology, Shantou University Medical College, Shantou, Guangdong, China; Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA, United States of America.
authors.forename: Qinsheng
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA, United States of America; Department of Obstetrics and Gynecology, Memorial Health University Medical Center, Savannah, GA, United States of America.
authors.forename: Jinping
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Surgery, Curtis and Elizabeth Anderson Cancer Institute, Memorial Health University Medical Center, Savannah, GA, United States of America.
authors.forename: Christopher
authors.initials: C
authors.lastname: Senkowski
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Zuoqing
authors.initials: Z
authors.lastname: Tang
authors.affiliation: School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, Jiangsu Province, China.
authors.forename: Jianhao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA, United States of America.
authors.forename: Tianhe
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA, United States of America.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Surgery, Curtis and Elizabeth Anderson Cancer Institute, Memorial Health University Medical Center, Savannah, GA, United States of America.
authors.forename: Karen
authors.initials: K
authors.lastname: Terry
authors.affiliation: Department of Surgery & Surgical Oncology, Beth Israel Medical Center, New York, NY, United States of America.
authors.forename: Steven
authors.initials: S
authors.lastname: Brower
authors.affiliation: Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA, United States of America.
authors.forename: Wayne
authors.initials: W
authors.lastname: Glasgow
authors.affiliation: Department of Histology and Embryology, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Haibin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Biomedical Science, Mercer University School of Medicine, Savannah, GA, United States of America; Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China; Department of Obstetrics and Gynecology, Memorial Health University Medical Center, Savannah, GA, United States of America.
authors.forename: Shi-Wen
authors.initials: SW
authors.lastname: Jiang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D015686:Gene Products, env / Q000235:genetics*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011257:Pregnancy Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D020079:Terminal Repeat Sequences; D046888:Tissue Array Analysis
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; D012333:RNA, Messenger; C405335:syncytin