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.
Highlights
Ranked as the fourth most deadly cancer for both females and males in the United States, pancreatic cancer patients have a 5-year overall survival rate lower than 6% [1, 2]
Results from real-time PCR indicated a significantly lower level of syncytin-1 mRNA in pancreatic adenocarcinoma compared to normal pancreatic tissues adjacent to cancer lesions (p
Densitometry analysis of the results indicated that, consistent with the mRNA levels, pancreatic carcinoma tissues expressed decreased syncytin-1 protein compared to cancer-adjacent normal tissues (Fig 2B)
Summary
Ranked as the fourth most deadly cancer for both females and males in the United States, pancreatic cancer patients have a 5-year overall survival rate lower than 6% [1, 2]. Multiple genetic and epigenetic alterations have been identified in pancreatic cancers, but the precise pathological mechanisms remain poorly understood. Numerous studies have focused on the genetic alterations and their involvement in pancreatic cancers, and multiple familial and somatic mutations were found to be contributing factors (reviewed in [4]). Mutations of KRAS oncogene and tumor suppressor genes such as p16, p53, DPC4, BRCA2, LKB1, and MKK4 were detected in pancreatic cancers at varied frequencies (reviewed in [2]). DNA hypermethylation was identified in precancerous lesions such as mucinous cystic neoplasms (MCNs), intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanIN) [8,9,10], pointing to an early involvement of epigenetic alterations in the development of pancreatic cancers
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