October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
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) |
NCI |
CANCER-10 |
Authors
- D Mendoza-Villanueva
- S Kim
- H Raza Ali
- B Kuppusamy
- S Sharan
- T Sarkar
- C Caldas
- E Sterneck
Abstract
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.
