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Analysis of C/EBPdelta Functions as a Candidate Tumor Suppressor in Hormone Receptor Positive Breast Cancer

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • D Mendoza-Villanueva
  • S Kim
  • H Raza Ali
  • B Kuppusamy
  • S Sharan
  • T Sarkar
  • C Caldas
  • E Sterneck


The transcription factor CCAAT/enhancer-binding protein delta (C/EBPdelta, CEBPD) is downregulated during breast cancer progression and exhibits many tumor suppressor-like activities.To assess the role of C/EBPdelta in human breast cancer, we analyzed tissue microarrays (TMA) by immunostaining, which revealed that C/EBPdelta protein was expressed in a subset of estrogen receptor (ER) positive (+) breast tumors and also correlated with progesterone expression. Furthermore, C/EBPdelta expression was associated with longer patient survival. These data indicate that C/EBPdelta expression is significantly associated with ER/PR(+) breast cancer and has potential as prognostic and/or predictive biomarker. To investigate the functions of C/EBPdelta, we silenced its expression in the ER/PR(+) MCF-7 tumor cell line. Here we show that C/EBPdelta attenuates proliferation and promotes estrogen-dependence of MCF7 cells. In this model, C/EBPdelta expression was induced by TAM, and C/EBPdelta augmented MCF-7 cell sensitivity to TAM. Using mRNA-Seq to characterize a C/EBPdelta-dependent gene signature, we found that many genes that were altered by C/EBPdelta-silencing were known p53 (TP53) targets. In addition we find that C/EBPdelta supports p53 protein expression and expression of the p53 target p21 as well as nuclear localization of p21. These data suggest that C/EBPdelta may augment tamoxifen response by promoting the p53-p21 tumor suppressor pathway.

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