Skip to Main Content

Skip Nav Destination

Abstracts Not Selected for Presentation| November 16, 2004

C/EBPδ Modulates Cell Growth, Differentiation and Apoptosis of Myeloid Leukemia, Prostate and Breast Cancer Cells.

Sigal Gery, PhD,

Sigal Gery, PhD *

(Intr. by H. Phillip Koeffler)¹ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ² Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ³ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ⁴ Hematology, University Hospital, Frankfurt/Main, Frankfurt/Main, Germany; ⁵ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA and ⁶ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Search for other works by this author on:

PubMed

Google Scholar

Sakae Stanosaki, MD,

Sakae Stanosaki, MD *

(Intr. by H. Phillip Koeffler)¹ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ² Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ³ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ⁴ Hematology, University Hospital, Frankfurt/Main, Frankfurt/Main, Germany; ⁵ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA and ⁶ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Search for other works by this author on:

PubMed

Google Scholar

Takayuki Ikezoe, MD,

Takayuki Ikezoe, MD *

(Intr. by H. Phillip Koeffler)¹ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ² Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ³ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ⁴ Hematology, University Hospital, Frankfurt/Main, Frankfurt/Main, Germany; ⁵ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA and ⁶ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Search for other works by this author on:

PubMed

Google Scholar

Wolf K. Hofmann, MD,

Wolf K. Hofmann, MD *

(Intr. by H. Phillip Koeffler)¹ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ² Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ³ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ⁴ Hematology, University Hospital, Frankfurt/Main, Frankfurt/Main, Germany; ⁵ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA and ⁶ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Search for other works by this author on:

PubMed

Google Scholar

Adrian F. Gombart, PhD,

Adrian F. Gombart, PhD *

(Intr. by H. Phillip Koeffler)¹ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ² Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ³ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ⁴ Hematology, University Hospital, Frankfurt/Main, Frankfurt/Main, Germany; ⁵ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA and ⁶ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Search for other works by this author on:

PubMed

Google Scholar

H. Phillip Koeffler, MD

H. Phillip Koeffler, MD *

(Intr. by H. Phillip Koeffler)¹ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ² Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ³ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; ⁴ Hematology, University Hospital, Frankfurt/Main, Frankfurt/Main, Germany; ⁵ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA and ⁶ Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Search for other works by this author on:

PubMed

Google Scholar

Blood (2004) 104 (11): 4300.

https://doi.org/10.1182/blood.V104.11.4300.4300

Abstract

C/EBPδ belongs to the family of highly conserved CCAAT/enhancer binding protein (C/EBP) transcription factors. Members of this family play a critical role in the regulation of mitotic growth arrest and differentiation in numerous cell types. To examine the consequences of C/EPBδ expression, we transfected C/EPBδ into CML myeloid leukemia (KCL22, K562), prostate (LNCaP, PC3, DU145), and breast (MCF-7, T47D, MDA-MB-231) cancer cell lines. C/EBPδ expression resulted in a proliferative arrest and an increase in apoptosis of the myeloid leukemia cells, as well as the prostate cells LNCaP and PC3, and the breast cells MCF-7 and T47D. In contrast, DU145 prostate and MDA-MB-231 breast cancer cells were not inhibited by C/EBPδ, indicating that the biologically properties of C/EBPδ depend upon its cellular context. We further studied the molecular mechanisms underlying the affect of C/EPBδ expression in CML leukemic cells. Myeloid differentiation of KCL22 and K562 blast cells as shown by morphologic changes and induction of secondary specific granule genes, occurred within 4 days of inducing expression of C/EBPδ. Furthermore, expression of C/EBPδ was associated with downregulation of c-Myc and cyclin E, and upregulation of the forkhead transcription factor FoxO1a (FKHR) and the cyclin-dependent kinase inhibitor p27Kip1. In addition, microarray analysis showed that C/EBPδ mRNA is upregulated during granulocytic differentiation of normal CD34+ bone marrow cells, suggesting that C/EBPδ is involved in lineage-specific differentiation. Taken together, these results show that expression of C/EBPδ in BCR-ABL-positive CML cells in blast crisis, is sufficient for neutrophil differentiation and suggest that ectopic induction of C/EBPδ in the blastic phase of CML, as well as in certain cases of prostate and breast cancers, may hold promising therapeutic potential.

Author notes

Corresponding author

2005, The American Society of Hematology

2004

Sign in via your Institution

Supplemental data