CCAAT/enhancer binding proteins in normal mammary development and breast cancer

Zahnow, Cynthia A.

doi:10.1186/bcr428

Cited by 90 publications

(72 citation statements)

References 61 publications

(91 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…C/EBPβ levels are indeed increased in many tumors (44), and gene expression databases have established that C/EBPβ is an indispensable effector of cyclin D1 transcriptional activity (45). Here, we demonstrated that ALK regulates CEBPB transcription and its protein levels mainly through STAT3.…”

Section: Discussionmentioning

confidence: 63%

Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and Bcl2A1 as critical target genes

et al. 2006

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 63%

Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and Bcl2A1 as critical target genes

et al. 2006

View full text Add to dashboard Cite

“…PLAC1 Is Selectively Activated by C/EBP␤ Isoform 2-Constitutive expression of C/EBP␤ has been reported in several human tissues, including liver, lung, ovary, placenta, and breast epithelial cells (27)(28)(29)(30). These data required reanalysis as they did not comply with the highly specific expression of C/EBP␤-regulated PLAC1 in the trophoblastic lineage of placental tissue.…”

Section: C/ebp␤ and Sp1 Are Required For Activation Of The Plac1mentioning

confidence: 68%

Selective Activation of Trophoblast-specific PLAC1 in Breast Cancer by CCAAT/Enhancer-binding Protein β (C/EBPβ) Isoform 2

Koslowski

Türeci²,

Biesterfeld

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

The trophoblast-specific gene PLAC1 (placenta-specific 1) is ectopically expressed in a wide range of human malignancies, most frequently in breast cancer, and is essentially involved in cancer cell proliferation, migration, and invasion. Here we show that basal activity of the PLAC1 promoter is selectively controlled by ubiquitous transcription factor SP1 and isoform 2 of CCAAT/enhancer-binding protein ␤ that we found to be selectively expressed in placental tissue and cancer cells. Binding of both factors to their respective elements within the PLAC1 promoter was essential to attain full promoter activity. Estrogen receptor ␣ (ER␣) signaling further augmented transcription and translation of PLAC1 and most likely accounts for the positive correlation between PLAC1 expression levels and the ER␣ status we observed in primary breast cancer specimens. DNA affinity precipitation and chromatin immunoprecipitation assays revealed that transactivation of the PLAC1 promoter by ligandactivated ER␣ is based on a nonclassical pathway independent of estrogen-response elements, by tethering of ER␣ to DNAbound CCAAT/enhancer-binding protein ␤-2, and SP1. Our findings provide first insight into a novel and hitherto unknown regulatory mechanism governing selective activation of trophoblast-specific gene expression in breast cancer.More than 100 years ago Scottish embryologist John Beard proposed a "trophoblastic theory of cancer" based on phenotypical similarities between the pregnancy trophoblast and cancer cells (1). In particular, these shared features are invasion in surrounding tissues (2), neovascularization (3), immunological escape (4), telomerase activity (5), aneuploidy (6), and epigenetic changes such as selective DNA hypermethylation (7). Based on these observations, it has long been speculated that cancer cells acquire characteristic traits by reactivation of embryonic or fetal gene programs, most prominently depicted by the ectopic production of oncofetal antigens, such as ␣-fetoprotein and carcinoembryonic antigen, and the aberrant production of chorionic gonadotropin and other trophoblastic hormones (8 -10). The knowledge of the molecular mechanisms underlying ectopic activation of placenta-specific genes in cancer, however, is sparse.In a recent study, we introduced PLAC1 as novel member of cancer-associated placental genes (11). The PLAC1 gene encodes a membrane-associated protein that is speculated to serve a receptor-like function modulating specific cell-cell or ligand-receptor interactions unique to the maternal-placental interface (12). PLAC1 is strictly confined to differentiated cells of the syncytiotrophoblast, in which it is expressed throughout human gestation, but underlies tight transcriptional repression in all other normal tissues (11-13). In the course of malignant transformation, however, PLAC1 is frequently activated and highly expressed in a variety of tumor types, in particular breast cancer. Applying RNA interference technology, we found that PLAC1 has a tumor-promoting role and is a criti...

show abstract

“…Its aberrant expression has been implicated in the pathogenesis of several epithelial tumors (7)(8)(9) and more recently, in NPM-ALK lymphoid transformation (5,10,11). In ALK þ ALCLs, C/EBPb expression depends on the tyrosine kinase activity of NPM-ALK and is transcriptionnally induced through the STAT3 signaling pathway, although no STAT3-specific binding sites have been observed in the C/EBP promoter region (5,10,11).…”

Section: Discussionmentioning

confidence: 99%

HuR-Mediated Control of C/EBPβ mRNA Stability and Translation in ALK-Positive Anaplastic Large Cell Lymphomas

Bergalet

Fawal

Lopez

et al. 2011

Molecular Cancer Research

View full text Add to dashboard Cite

The CCAAT/enhancer-binding protein b (C/EBPb) plays a major role in the pathogenesis of anaplastic large cell lymphomas (ALCL) that express the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) tyrosine kinase (ALK þ ). Although ALK-mediated C/EBPb transcriptional activation has been reported, C/EBPb mRNA possesses U-and AU-rich domains in its 3 0 -untranslated region (3 0 -UTR) that might be privileged targets for posttranscriptional control in ALK þ ALCLs. The purpose of this study was to explore this possibility. By using human ALCL-derived cells and a murine model of ALK-transformed cells, we show that the AU-binding protein HuR binds to the 3 0

show abstract

CCAAT/enhancer binding proteins in normal mammary development and breast cancer

Cited by 90 publications

References 61 publications

Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and Bcl2A1 as critical target genes

Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and Bcl2A1 as critical target genes

Selective Activation of Trophoblast-specific PLAC1 in Breast Cancer by CCAAT/Enhancer-binding Protein β (C/EBPβ) Isoform 2

HuR-Mediated Control of C/EBPβ mRNA Stability and Translation in ALK-Positive Anaplastic Large Cell Lymphomas

Contact Info

Product

Resources

About