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Entity | Ulnar-mammary syndrome |
Note | Results from congenital mutations in a single copy of the human TBX3 gene. |
Disease | Characterised by posterior limb abnormalities, such as malformed ulna and posterior digits, hypoplasia and/or dysfunction of the mammary and apocrine glands, absent axillary hair, abnormal dentition, delayed puberty in males and genital anomalies (Bamshad et al., 1996; Bamshad et al., 1997). |
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Entity | Breast cancer |
Note | Breast cancer lines screened by real time PCR analysis displayed increased expression of TBX3 in 15 of 28 cell lines tested (Fan et al., 2004). When TBX3 expression was examined by immunohistochemistry in breast tumour tissues, the results showed that levels of TBX3 protein were higher in tumour tissue compared to adjacent normal tissue, with increased cytoplasmic localisation. |
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Entity | Pancreatic cancer |
Note | Microarray analyses comparing non-metastatic and metastatic pancreatic endocrine neoplasms revealed that TBX3 expression is upregulated in the latter tumour type (Hansel et al., 2004). |
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Entity | Ovarian cancer |
Note | Using 2D gel electrophoresis and matrix-assisted laser desorption/ionization (MALDI) time of flight (TOF) mass spectrometry, a truncated form of TBX3 was detected in blood plasma from ovarian cancer patients (Lomnytska et al., 2006). |
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Entity | Liver cancer |
Note | Increased TBX3 expression was shown to correlate with a mutant active form of β-catenin in both human and mouse hepatocellular carcinomas (HCCs) and human hepatoblastomas. Renard et al. (2007) demonstrated TBX3 to be involved in β-catenin's activation of cell proliferation in the human hepatoma cell line HepG2. Using in vitro assays they showed that expression of mutant β-catenin upregulated TBX3 expression and that this was due to direct binding of active β-catenin together with its co-activator T-cell factor (Tcf) to a Tcf-binding element in the TBX3 promoter (Renard et al., 2007). |
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Entity | Glioblastoma |
Note | Genome-wide DNA methylation profiling of 55 glioblastoma tissue samples compared to non-neoplastic brains revealed that methylation of TBX3 correlated with decreased overall survival, identifying it as a potential independent prognostic marker (Etcheverry et al., 2010). |
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Entity | Gastric cancer |
Note | Genome-wide screening identified TBX3 to be epigenetically silenced in the gastric cancer cell line AGS and the TBX3 gene was shown to be methylated in 7 out of 10 primary gastric cancers (Yamashita et al., 2006). |
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Entity | Uterine cervical cancer |
Note | TBX3 expression was shown to be downregulated in microarray analyses comparing lymph node positive to lymph node negative cervical tumours. A significant correlation was observed between low TBX3 expression and the metastatic phenotype. In addition, multivariate analysis identified TBX3 as a potential independent prognostic marker for this cancer (Lyng et al., 2006). |
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Entity | Melanoma |
Note | In 2004, Hoek et al. showed that compared to normal melanocytes TBX3 expression was upregulated in at least 4 of 6 melanoma cell lines tested and Rodriguez et al. (2008) later demonstrated increased TBX3 protein levels in 6 out of 12 melanoma cell lines. Furthermore, TBX3 was shown to contribute to melanoma formation, migration and invasion by a process involving its ability to repress the cell adhesion molecule E-cadherin (Rodriguez et al., 2008; Peres et al., 2010). |
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Entity | Head and neck squamous cell cancer |
Note | TBX3 is upregulated in head and neck squamous cell carcinoma (HNSCC) cell lines and tissues (Humtsoe et al., 2011; Burgucu et al., 2012). The study by Humtsoe et al. shows that TBX3 expression is specifically upregulated in HNSCC cells which display characteristics of epithelial to mesenchymal transition (EMT). Interestingly, however they show that TBX3 promotes cell survival and to a lesser extent, cell invasion in these cells (Humtsoe et al., 2011). This is consistent with the results of Burgucu et al. (2012) which demonstrate that TBX3 represses the tumour suppressor, phosphatase and TENsin homolog (PTEN). |
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PMID 8878690 |
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The spectrum of mutations in TBX3: Genotype/Phenotype relationship in ulnar-mammary syndrome. |
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PMID 11748239 |
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Hum Mol Genet. 2001 Oct 1;10(21):2403-13. |
PMID 11689487 |
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Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome. |
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PMID 12668638 |
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DNA methylation in glioblastoma: impact on gene expression and clinical outcome. |
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PMID 21156036 |
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TBX3 and its isoform TBX3+2a are functionally distinctive in inhibition of senescence and are overexpressed in a subset of breast cancer cell lines. |
Fan W, Huang X, Chen C, Gray J, Huang T. |
Cancer Res. 2004 Aug 1;64(15):5132-9. |
PMID 15289316 |
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Met proto-oncogene and insulin-like growth factor binding protein 3 overexpression correlates with metastatic ability in well-differentiated pancreatic endocrine neoplasms. |
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PMID 15448002 |
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Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. |
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PMID 15289333 |
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TBX3 and its splice variant TBX3 + exon 2a are functionally similar. |
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PMID 18444963 |
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Transcriptional profiling identifies upregulated genes following induction of epithelial-mesenchymal transition in squamous carcinoma cells. |
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Exp Cell Res. 2012 Feb 15;318(4):379-90. doi: 10.1016/j.yexcr.2011.11.011. Epub 2011 Nov 29. |
PMID 22154512 |
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Tbx3 expression is related to apoptosis and cell proliferation in rat bladder both hyperplastic epithelial cells and carcinoma cells. |
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PMID 15694670 |
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The Brachyury gene encodes a novel DNA binding protein. |
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PMID 8344258 |
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The T-box repressors TBX2 and TBX3 specifically regulate the tumor suppressor gene p14ARF via a variant T-site in the initiator. |
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J Biol Chem. 2002 Jul 19;277(29):26120-7. Epub 2002 May 8. |
PMID 12000749 |
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Increased expression of cSHMT, Tbx3 and utrophin in plasma of ovarian and breast cancer patients. |
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Int J Cancer. 2006 Jan 15;118(2):412-21. |
PMID 16049973 |
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Gene expressions and copy numbers associated with metastatic phenotypes of uterine cervical cancer. |
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The Highly Homologous T-Box Transcription Factors, TBX2 and TBX3, Have Distinct Roles in the Oncogenic Process. |
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Tbx3 is a downstream target of the Wnt/beta-catenin pathway and a critical mediator of beta-catenin survival functions in liver cancer. |
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Tbx3 represses E-cadherin expression and enhances melanoma invasiveness. |
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