VentX, a novel lymphoid-enhancing factor/T-cell factor-associated transcription repressor, is a putative tumor suppressor.
Lymphoid-enhancing factor/T-cell factors (LEF1/TCF) are a high-mobility group of transcriptional factors that play essential roles in cell fate determination during early embryogenesis and ontogenesis. Aberrant activations of LEF1/TCF-mediated transcription have been implicated in a variety of malignancies. Our recent studies on vertebrate embryogenesis identified Xom, a homeobox protein of the bone morphogenetic protein 4 pathway, as a novel LEF/TCF-associated transcriptional modulator. Here, we report that VentX, a human Xom homologue, is a LEF/TCF-associated inhibitor of canonical Wnt/beta-catenin signaling and a negative regulator of cell proliferation. VentX is predominantly expressed in hematopoietic cells, and its expression is significantly downregulated in chronic lymphocytic leukemia. Altered expression of VentX is associated with corresponding changes of LEF/TCF target oncogenes such as cyclin D1, suggesting a potential role of VentX in the clinical behavior of hematopoietic malignancies.
Gao
Hong
H
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Le
Yi
Y
Wu
Xiaoming
X
Silberstein
Leslie E
LE
Giese
Roger W
RW
Zhu
Zhenglun
Z
D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D018398:Homeodomain Proteins; C408346:VENTX protein, human