CCAAT/enhancer binding protein delta (C/EBPδ)demonstrates a dichotomous role in tumour initiation and promotion of epithelial carcinoma

Ramlogan Sowamber, Rania Chehade, Mahmoud Bitar, Leah V. Dodds, Anca Milea, Brian Slomovitz, Patricia A. Shaw, Sophia George

Research output: Contribution to journalArticle

Abstract

Background: CCAAT/enhancer binding protein delta (C/EBPδ,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 carcinomas of the ovary (HGSC). Overexpression of C/EBPδ in different tumours, such as glioblastoma and breast cancer either promotes tumour progression or inhibits growth and has low expression in normal tissue until activated by cytotoxic stressors. Methods: Higher overall expression of C/EBPδ in the luteal phase of the menstrual cycle prompted us to investigate the role of C/EBPδ in carcinogenesis. In vitro experiments were conducted in fallopian tube cell samples and cancer cell lines to investigate the role of C/EBPδ in proliferation, migration, and the epithelial to mesenchymal transition. Findings: Expression of C/EBPδ induced premature cellular arrest and decreased soft agar colony formation. Loss of C/EBPδ in epithelial cancer cell lines did not have significant effects on proliferation, yet overexpression demonstrated downregulation of growth, similar to normal fallopian tube cells. C/EBPδ promoted a partial mesenchymal to epithelial (MET)phenotype by upregulating E-cadherin and downregulating Vimentin and N-cadherin in FTE cells and increased migratory activity, which suggests a regulatory role in the epithelial-mesenchymal plasticity of these cells. Interpretation: Our findings suggest that C/EBPδ regulates the phenotype of normal fallopian tube cells by acting on downstream regulatory factors that are implicated in the development of ovarian serous carcinogenesis. Fund: This study was funded by the CDMRP Ovarian Cancer program (W81WH-0701-0371, W81XWH-18-1-0072), the Princess Margaret Cancer Centre Foundation, Foundation for Women's Cancer – The Belinda-Sue/Mary-Jane Walker Fund, Colleen's Dream Foundation and Sylvester Comprehensive Cancer Center.

Original languageEnglish (US)
JournalEBioMedicine
DOIs
StatePublished - Jan 1 2019

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CCAAT-Enhancer-Binding Protein-delta
Tumors
Carcinoma
Neoplasms
Fallopian Tubes
Down-Regulation
Cadherins
Carcinogenesis
Cells
Phenotype
Cell Line
Leucine Zippers
Epithelial-Mesenchymal Transition
Luteal Phase
Vimentin
Glioblastoma
Growth
Ovarian Neoplasms
Agar
Plasticity

Keywords

  • C/EBPδ
  • Epithelial to mesenchymal transition
  • Fallopian tube epithelia
  • High-grade serous ovarian cancer

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

CCAAT/enhancer binding protein delta (C/EBPδ)demonstrates a dichotomous role in tumour initiation and promotion of epithelial carcinoma. / Sowamber, Ramlogan; Chehade, Rania; Bitar, Mahmoud; Dodds, Leah V.; Milea, Anca; Slomovitz, Brian; Shaw, Patricia A.; George, Sophia.

In: EBioMedicine, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Background: CCAAT/enhancer binding protein delta (C/EBPδ,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 carcinomas of the ovary (HGSC). Overexpression of C/EBPδ in different tumours, such as glioblastoma and breast cancer either promotes tumour progression or inhibits growth and has low expression in normal tissue until activated by cytotoxic stressors. Methods: Higher overall expression of C/EBPδ in the luteal phase of the menstrual cycle prompted us to investigate the role of C/EBPδ in carcinogenesis. In vitro experiments were conducted in fallopian tube cell samples and cancer cell lines to investigate the role of C/EBPδ in proliferation, migration, and the epithelial to mesenchymal transition. Findings: Expression of C/EBPδ induced premature cellular arrest and decreased soft agar colony formation. Loss of C/EBPδ in epithelial cancer cell lines did not have significant effects on proliferation, yet overexpression demonstrated downregulation of growth, similar to normal fallopian tube cells. C/EBPδ promoted a partial mesenchymal to epithelial (MET)phenotype by upregulating E-cadherin and downregulating Vimentin and N-cadherin in FTE cells and increased migratory activity, which suggests a regulatory role in the epithelial-mesenchymal plasticity of these cells. Interpretation: Our findings suggest that C/EBPδ regulates the phenotype of normal fallopian tube cells by acting on downstream regulatory factors that are implicated in the development of ovarian serous carcinogenesis. Fund: This study was funded by the CDMRP Ovarian Cancer program (W81WH-0701-0371, W81XWH-18-1-0072), the Princess Margaret Cancer Centre Foundation, Foundation for Women's Cancer – The Belinda-Sue/Mary-Jane Walker Fund, Colleen's Dream Foundation and Sylvester Comprehensive Cancer Center.",
keywords = "C/EBPδ, Epithelial to mesenchymal transition, Fallopian tube epithelia, High-grade serous ovarian cancer",
author = "Ramlogan Sowamber and Rania Chehade and Mahmoud Bitar and Dodds, {Leah V.} and Anca Milea and Brian Slomovitz and Shaw, {Patricia A.} and Sophia George",
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AU - Sowamber, Ramlogan

AU - Chehade, Rania

AU - Bitar, Mahmoud

AU - Dodds, Leah V.

AU - Milea, Anca

AU - Slomovitz, Brian

AU - Shaw, Patricia A.

AU - George, Sophia

PY - 2019/1/1

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