Disease relevance of Tcf7

• Increased cytoplasmic beta-catenin levels and the associated nuclear beta-catenin/T-cell factor (Tcf)-lymphoid enhancer factor (LEF) complex formation have been frequently found in colon cancer [1].
• These results suggest that the reduced APC protein level increases intestinal polyp multiplicity through quantitative stimulation of the beta-catenin/T-cell factor transcription [2].
• Fresh mesothelioma cells (effusion derived), as well as LRK1A, REN, and H513 cell lines showed a significant fold increase (1.5-2.4-fold, P < 0.01) in Tcf-dependent transcriptional activity of beta-catenin [3].
• However, additional deficiency of Tcf-1 completely blocks normal mammary development and results in acanthoma [4].
• Conclusions:S100A4 is a direct beta-catenin/TCF target, induces migration and invasion in vitro and metastasis in vivo, and has value for prognosis of metastasis formation in colon cancer patients [5].

High impact information on Tcf7

• Maturity-onset diabetes of the young type 3 (MODY3) is caused by haploinsufficiency of hepatocyte nuclear factor-1alpha (encoded by TCF1) [6].
• Suppressor T-cell inactivation of a helper T-cell factor [7].
• Together, these data provide evidence for a redundant role of LEF-1 and TCF-1 in Wnt signaling during mouse development [8].
• Redundant regulation of T cell differentiation and TCRalpha gene expression by the transcription factors LEF-1 and TCF-1 [9].
• Thus, TCF-1, upon association with beta-catenin, transiently ensures the survival of immature T cells, which enables them to generate and edit T cell receptor (TCR) alpha chains and attempt TCR-mediated positive selection [10].

Chemical compound and disease context of Tcf7

• Prostaglandin E2 Stimulates the beta-catenin/T cell factor-dependent transcription in colon cancer [11].
• Picryl chloride factor (PC1-F) is an antigen (TNP hapten)-binding T cell factor that initiates PC1 contact sensitivity (CS) [12].
• This report defines a methodology for the production and characterization of an antigen-specific, monoclonal T cell hybrid-derived suppressor T cell factor (TsF) that suppresses the passive transfer of 2,4-dinitrofluorobenzene (DNFB) contact hypersensitivity [13].
• Picryl (trinitrophenyl) chloride (PCL) contact sensitization of mice induces T cells that release an antigen-binding T cell factor (PCLF) that plays an important role in the initiation of contact sensitivity responses, in part via activation of mast cells [14].
• The presence of this T cell factor in the serum of actively sensitized mice provides a means to sensitize tissues throughout the body for this required, initial, serotonin-dependent component of delayed-type hypersensitivity reactions [15].

Biological context of Tcf7

• Transfection studies suggest that Tcf7 modulates BMP2-induced osteoblast differentiation [16].
• Our findings expand the repertoire of ligands that induce beta-catenin/TCF-dependent gene activation and implicate the presence of active beta-catenin-dependent gene activation in a Wnt-free biological context [17].
• T cell factor / lymphocyte enhancer factor (Tcf/Lef) transcription factors complex with the transcriptional co-activator beta-catenin to transduce Wnt signals in a variety of developmental systems [18].
• Members of the TCF/LEF (T cell factor / lymphoid enhancer factor) family of DNA-binding factors play important roles during embryogenesis, the establishment and/or maintenance of self-renewing tissues such as the immune system and for malignant transformation [19].
• Increasing anti-apoptotic effectors in thymocytes by the use of a Bcl-2 transgene rescued TCF-1-deficient DP thymocytes from apoptosis [10].

Anatomical context of Tcf7

• Cells constitutively expressing the regulated gene Tcf7 were used to investigate its influence on BMP-induced osteoblast differentiation [16].
• Together, these data show that LEF-1 and TCF-1 are redundant in the regulation of T cell differentiation and gene expression [9].
• These findings suggest common and distinct functions of TCF-1 and LEF-1 during lymphocyte development [19].
• Collectively these findings suggest (1) a functional role for Wnt-producing thymic epithelium in determining TCF/LEF-mediated transcriptional regulation in Fz-bearing thymocytes, and (2) a role for defined Wnt-Fz interactions at successive stages of thymocyte maturation [20].
• Second, by high stringency Northern blotting and in situ hybridization, TCF-1 expression was shown to be confined to the thymus and to the T cell areas of the spleen [21].

Associations of Tcf7 with chemical compounds

• Recently it was reported that beta-catenin interacts with retinoic acid receptor in a retinoid-dependent manner, reducing beta-catenin/TCF regulated transcription [22].
• We find that cells respond to H(2)O(2) stimulation by activating TCF [23].
• DMSO provoked T cell factor-dependent transcriptional activity; thus, induction of Wnt proteins by DMSO was functionally coupled [24].
• We identified ICG-001, a small molecule that down-regulates beta-catenin/T cell factor signaling by specifically binding to cyclic AMP response element-binding protein [25].
• When ectopically expressed, the silencing mediator for retinoid and thyroid receptors/histone deacetylase 1-associated repressor protein (SHARP) protein potently enhanced beta-catenin/TCF transcription of a model reporter gene and cellular target genes [26].

Physical interactions of Tcf7

• Aberrant transactivation of a certain set of target genes by the beta-catenin and T-cell factor/lymphoid enhancer factor complex has been considered crucial for the initiation of intestinal tumorigenesis [27].
• Cloning of murine TCF-1, a T cell-specific transcription factor interacting with functional motifs in the CD3-epsilon and T cell receptor alpha enhancers [21].
• Replication of VRX-009 is restricted to cells with a deregulated wnt signal transduction pathway by replacement of the wild-type Ad E4 promoter with a synthetic promoter consisting of five consensus binding sites for the T-cell factor transcription factor [28].

Regulatory relationships of Tcf7

• First, conditioned medium containing Cristin/R-spondin proteins effectively induced reporter activity in a TCF-binding site-dependent manner [17].
• Lithium treatment of BAEC induced beta-catenin stabilization but failed to activate the transcriptional activity of the beta-catenin/T-cell factor complex [29].
• Inhibitor of beta-catenin and T cell factor (ICAT) inhibits Wnt signaling by interfering with the interaction between beta-catenin and T cell factor [30].
• This IFN-beta-induced suppressor T-cell factor (IFN-TsF) has properties in common with SIRS [31].
• We found that first-order suppressor T-cell factor ( TsF1 ) obtained from anti-mu treated animals expresses an Igh restriction pattern distinct from that observed with TsF1 from normal untreated mice [32].

Other interactions of Tcf7

• Microarray and subsequent expression analyses in mice identified two transcription factors, Hey1 and Tcf7, with in vitro and in vivo expression characteristics very similar to Cbfa1 [16].
• A contig of 24 YACs and 13 P1 clones has been assembled and spans approximately 3 Mb from Flt4 to Tcf7 [33].
• A major downstream consequence of Wnt-1 signalling is the activation of beta-catenin/T-cell factor (TCF)-mediated transcription [34].
• We have conditionally inactivated Apc in both the presence and absence of Tcf-1 to examine the function of these genes in both normal and neoplastic development [4].
• We demonstrate here that LRP5/Frat1 interaction is involved in beta-catenin nuclear translocation and TCF-1 transcriptional activation [35].

Analytical, diagnostic and therapeutic context of Tcf7

• For several of these target genes, we validated that they are true Wnt/beta-catenin/TCF target genes using real-time quantitative PCR and reporter gene assays [36].
• We identified target genes of the Wnt/beta-catenin/TCF pathway in the most immature (CD4-CD8-CD34+) thymocytes using Affymetrix DNA microarrays in combination with three different functional assays for in vitro induction of Wnt signaling [36].
• beta-Catenin functions as a transducer of Wnt signals to the nucleus, where it interacts with the T cell factor (TCF) family of DNA binding proteins to regulate gene expression [37].
• By chromatin immunoprecipitation, recruitment of beta-catenin and TCF1 to the endogenous Runx2 gene is shown [38].
• CTP1 may form the basis for effective, targeted gene therapy of metastatic colon cancer and other tumors with deregulated beta-catenin/T cell factor [39].

References