Aberrant Expression And Its Mechanism Of SFRP1 And SFRP2-antagonists Of Wnt In Pancreatic Carcinoma

BackgroundThe canonical Wnt signaling pathway takes important roles in embryonic development, cell proliferation and cell differentiation. Defects in this pathway have been implicated in the pathogenesis of various types of tumors in human beings. Secreted frizzled - related proteins (SFRPs) are a family of Wnt antagonists that harbours a cyteine -rich domain (CRD) homologous to the frizzled receptors. SFRPs are able to bind Wnt proteins in the extracellular compartment, thereby inhibiting ligand - receptor interaction and signal transduction.SFRP1 is a putative inhibitor of Wnt signaling. Its expression is frequently lost or strongly reduced in some tumors, including breast, colorectal, prostate and ovarian cancers. The SFRP1 gene is located in a chromosomal region that is frequently deleted in some tumors and is thought to harbour a tumor suppressor gene. To be a member of SFRPs family, some studies indicated that silencing of SFRP2 expression played an important role in the carcinogenesis of esophagus and colorectal tumors.In this study, we aim to investigate the expressions of SFRP1 and SFRP2 in pancreatic tumors and matched normal pancreatic tissues, analyze the mechanism of gene silencing. Meanwhile, analyze the relationship between the aberrant expression and clinical pathologic characteristics.MethodsMatched tumour/normal samples of pancreatic cancer specimens (n =36) and normal pancreatic tissues (n =6) analyzed in this study were obtained frompatients at the departments of general surgery at 2n affiliated hospital, China medical university. We detected the protein expression of SFRPl and SFRP2 with immunohistochemical method, detect the level of mRNA with RT - PCR method, and the status of methylation with the methylation - specific PCR method. The clinical pathologic characteristics of all the patients were summarized to find the relationship between the loss of expression of the both genes and their clinical pathologic characteristics.ResultsIn normal pancreatic tissues, positive expression of SFRPl protein and its mRNA can be tested. No methyltion was found. 5 out of 6 took on expression for SFRP2 protein and its mRNA. Methyltion of promoter was tested in one sample with loss of SFRP2 expression. The loss of SFRPl and SFRP2 expression were detected in 20 and 16 pancreatic cancer samples respectively. In matched normal tissues, the loss of expression occurred in 6 and 7 samples. The difference between cancer and matched normal tissue is significant. Methyltion of SFRPl promoter was found in 23 pancreatic cancer samples and in 8 matched normal tissues, that of SFRP2 were 19 and 11 respectively . The difference between cancer and matched normal tissue is significant. The loss of SFRPl expression is correlated with status of methyltion, TNM stages and lymph node metastasis of tumors. The loss of SFRP2 expression is correlated with status of methyltion.Conclusion1. In normal pancreatic tissue, no methyltion of SFRPl promoter is found, and it rarely happens for SFRP2.2. The loss of expression of SFRPl and SFRP2 may take place in both pancreatic cancer and matched normal tissue, but it is much more frequent in the tumors.3. The mechanism of loss of expression is due to the methyltion of promoter.4. The loss of SFRPl expression may be correlated with the greater invasivecapacity of the cancer and associated with unfavorable prognosis.