C/EBPδ demonstrates a dichotomous role in tumor initiation and promotion of epithelial carcinoma

Abstract

C/EBP{delta} (CEBPD), a gene part of the highly conserved basic-leucine zipper (b-ZIP) domain of transcriptional factors, is downregulated in 65% of high grade serous carcinoma of the ovary (HGSC). Overexpression of C/EBP{delta} in different tumors as glioblastoma and breast cancer either promotes tumor progression or inhibits growth. Despite these contradictory roles in different cancer types, we show that C/EBP{delta} overexpression has a consistent function of downregulating proliferation and promoting migration in fallopian tube epithelial cells (FTE). We show that the FTE have both mesenchymal and epithelial cell characteristics. Further, our data supports a role for C/EBP{delta} as an early regulatory transcriptional factor that promotes a mesenchymal to epithelial (MET) phenotype by upregulating E-cadherin and downregulating vimentin and N-cadherin in FTE cells. We demonstrate that overexpression of C/EBP{delta} in ovarian and breast cancer cell lines have consistent effects and phenotype as the FTE cells. Our findings suggest a role for C/EBP{delta} in the early events of ovarian serous carcinogenesis which may be used to help further understand how the disease develops from a premalignant cells.