Regulation of Vascular Endothelial Growth Factor D by Orphan Receptors Hepatocyte Nuclear Factor-4α and Chicken Ovalbumin Upstream Promoter Transcription Factors 1 and 2

Schäfer, Georgia; Wissmann, Christoph; Hertel, Johannes; Lunyak, Victoria V.; Höcker, Michael

doi:10.1158/0008-5472.can-07-5136

Cited by 25 publications

(20 citation statements)

References 54 publications

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“…Studies showed the involvement of COUP-TF1 in cell differentiation and growth in endometrial and ovarian cancer cells [27]. Recently, this gene was found to play a role in lymphangeogenesis via regulation of the vascular endothelial growth factor (VEGF) in cancer [28]. HOXD10 belongs to the HOX regulatory family of genes that encode transcription factors which are essential during embryonic development [34].…”

Section: Discussionmentioning

confidence: 99%

Microarray Analysis Reveals Distinct Gene Expression Profiles Among Different Tumor Histology, Stage and Disease Outcomes in Endometrial Adenocarcinoma

et al. 2010

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BackgroundEndometrial cancer is the most common gynecologic malignancy in developed countries and little is known about the underlying mechanism of stage and disease outcomes. The goal of this study was to identify differentially expressed genes (DEG) between late vs. early stage endometrioid adenocarcinoma (EAC) and uterine serous carcinoma (USC), as well as between disease outcomes in each of the two histological subtypes.Methodology/Principal FindingGene expression profiles of 20 cancer samples were analyzed (EAC = 10, USC = 10) using the human genome wide illumina bead microarrays. There was little overlap in the DEG sets between late vs. early stages in EAC and USC, and there was an insignificant overlap in DEG sets between good and poor prognosis in EAC and USC. Remarkably, there was no overlap between the stage-derived DEGs and the prognosis-derived DEGs for each of the two histological subtypes. Further functional annotation of differentially expressed genes showed that the composition of enriched function terms were different among different DEG sets. Gene expression differences for selected genes of various stages and outcomes were confirmed by qRT-PCR with a high validation rate.ConclusionThis data, although preliminary, suggests that there might be involvement of distinct groups of genes in tumor progression (late vs. early stage) in each of the EAC and USC. It also suggests that these genes are different from those involved in tumor outcome (good vs. poor prognosis). These involved genes, once clinically verified, may be important for predicting tumor progression and tumor outcome.

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Section: Discussionmentioning

confidence: 99%

Microarray Analysis Reveals Distinct Gene Expression Profiles Among Different Tumor Histology, Stage and Disease Outcomes in Endometrial Adenocarcinoma

et al. 2010

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“…For example, aberrant CREB signaling is frequently reported in leukemia cells and endocrine tumors (36). COUP-TF may induce oncogenic cell signaling through multiple pathways including its positive regulation on the transcription of vascular endothelial factors C and D (37, 38). STAT5A/B are known to play a role in pathogenesis of both prostate cancer and breast cancer (39), and HNF-4 has been shown to be dysregulated in a variety of cancers, including gastric, hepatocellular, and colorectal carcinomas (40).…”

Section: Biochemical Characterization Of Muc13mentioning

confidence: 99%

Mucin 13: Structure, Function, and Potential Roles in Cancer Pathogenesis

Maher

Gupta

Nagata

et al. 2011

Molecular Cancer Research

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Mucin 13 (MUC13) is a high-molecular-weight transmembrane glycoprotein that is frequently and aberrantly expressed in a variety of epithelial carcinomas, including gastric, colorectal, and ovarian cancers. On the basis of the high expression of MUC13 in cancer cells as well as recent laboratory findings suggesting a malignant phenotype of MUC13-transfected cell lines, the oncogenic potential of MUC13 has emerged. The various functional domains of MUC13 may confer oncogenic potential to MUC13. For example, the bulky extracellular domain with extensive modification with glycan chains may prevent cell–cell and cell–extracellular matrix binding whereas the cytoplasmic tail containing serine and tyrosine residues for potential phosphorylation may participate in cell signaling. MUC13 exhibits the characteristics suitable as an early marker for cancer screening and presents a promising target for antibody-guided targeted therapy.

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“…A very strong binding of the corepressor was found in the ER+ cells when the proximal −423/−119 region of the VEGF-D gene was analyzed and again NCoR binding to these sequences was very low in the ER − cells. However, NCoR was not recruited to the −608/−430 region of the VEGF-D gene, previously proposed to be necessary for VEFG-D transcription [39, 40] (Figure 1B). …”

Section: Resultsmentioning

confidence: 90%

“…Although other factors different from NCoR could be responsible for the negative association with lympangiogenic gene expression in these independently-derived cell lines, the inverse relationship observed suggested that NCoR could repress VEGF-C and VEGF-D gene transcription. Proximal promoter sequences appear to play an important role in the control of VEGF-C and VEGF-D transcription [39, 40]. To analyze if NCoR could bind to the regulatory region of these lymphangiogenic genes, we performed chromatin immunoprecipitation (ChIP) assays with an NCoR antibody and two different fragments of the 5′-flanking regions of these genes.…”

Section: Resultsmentioning

confidence: 99%

The nuclear corepressor 1 and the thyroid hormone receptor β suppress breast tumor lymphangiogenesis

et al. 2016

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Vascular Endotelial Growth Factors C and D (VEGF-C and VEGF-D) are crucial regulators of lymphangiogenesis, a main event in the metastatic spread of breast cancer tumors. Although inhibition of lymphangiogenic gene expression might be a useful therapeutic strategy to restrict the progression of cancer, the factors involved in the transcriptional repression of these genes are still unknown. We have previously shown that Nuclear Receptor Corepressor 1 (NCoR) and the thyroid hormone receptor β1 (TRβ) inhibit tumor invasion. Here we show that these molecules repress VEGF-C and VEGF-D gene transcription in breast cancer cells, reducing lymphatic vessel density and sentinel lymph node invasion in tumor xenografts. The clinical significance of these results is stressed by the finding that NCoR and TRβ transcripts correlate negatively with those of the lymphangiogenic genes and the lymphatic vessel marker LYVE-1 in human breast tumors. Our results point to the use of NCoR and TRβ as potential biomarkers for diagnosis or prognosis in breast cancer and suggest that further studies of these molecules as potential targets for anti-lymphangiogenic therapy are warranted.

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Regulation of Vascular Endothelial Growth Factor D by Orphan Receptors Hepatocyte Nuclear Factor-4α and Chicken Ovalbumin Upstream Promoter Transcription Factors 1 and 2

Cited by 25 publications

References 54 publications

Microarray Analysis Reveals Distinct Gene Expression Profiles Among Different Tumor Histology, Stage and Disease Outcomes in Endometrial Adenocarcinoma

Microarray Analysis Reveals Distinct Gene Expression Profiles Among Different Tumor Histology, Stage and Disease Outcomes in Endometrial Adenocarcinoma

Mucin 13: Structure, Function, and Potential Roles in Cancer Pathogenesis

The nuclear corepressor 1 and the thyroid hormone receptor β suppress breast tumor lymphangiogenesis

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