English abstract
Introduction: Epithelial Ovarian Cancer (EOC) is a most lethal cancer among gynecologic cancers. Annually, 22000 women are diagnosed with EOC in United States. The survival rate of patients in advanced stage is lower than 25%, with very poor outcomes. Therefore, detection of disease in early stage and understanding of genetic pathways involved in the EOC pathogenesis are very important to finding out good predictable markers. Previous studies have reported the overexpression of the transcription factor E2F5 in early and late stages of EOC, suggesting its putative role as a biomarker. SOCS3 gene, a key regulator for JAK/STAT pathway, responsible for inflammation and proliferation response, was found to be regulated by E2F5 and its down regulation seems to have a role in the pathogenesis of different tumors including gastric and pancreatic cancers.
Aim: in this project, we aim to investigate the involvement of SOCS3 gene in EOC by measuring its expression in ovarian cancer cell line and tissues compared to normal ovarian tissues. Further, we aimed to examine methylation status in both ovarian cell
lines and ovarian tissues. Methods: Real time qPCR was used to measure gene expression using Taq Man gene
expression assay. Five cell lines (MCAS, OVSAHO, OV 2008, A2780s and A2780cp) and 19 tissue samples with different histopathology types (6 normal, 4 benign, 5 borderline and 4 high grade serous) were used in this project. Methylation
status analysis was performed by methylation specific PCR.
Results: OVSAHO, OV2008 and A2780s cell lines showed down regulation of SOCS3 expression compared to normal. Benign, borderline and HGS tissues also obtain significant down regulation in SOCS3 expression. Analysis of methylation pattern represented no hypermethylation in both cell lines and tissues.
Conclusion: Down regulation of SOCS3 gene expression was detected in cell lines and tissues samples indicate a putative role in the pathogenesis of EOC. Other epigenetics mechanisms such as micro-RNAs are involved in the regulation of SOCS3
expression in addition to hypermethylation and therefore, further study is needed to validate these mechanisms.
