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bioRxiv · 10.1101/528885

C/EBPδ demonstrates dichotomous tumor initiation and promotion in high grade serous ovarian carcinogenesis

Sowamber, R.·Chehade, R.·Bitar, M.·Dodds, L.·Milea, A.·Shaw, P.·George, S. H.
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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.

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Sowamber, R., Chehade, R., Bitar, M., Dodds, L., Milea, A., Shaw, P., George, S. H.. 2019-01-23. C/EBPδ demonstrates dichotomous tumor initiation and promotion in high grade serous ovarian carcinogenesis. https://doi.org/10.1101/528885

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