Cancer research (Chicago, Ill.), 2003-06, Vol.63 (12), p.3145-3153
2003
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- Autor(en) / Beteiligte
- Titel
- β-catenin regulates vascular endothelial growth factor expression in colon cancer
- Ist Teil von
- Cancer research (Chicago, Ill.), 2003-06, Vol.63 (12), p.3145-3153
- Ort / Verlag
- Philadelphia, PA: American Association for Cancer Research
- Erscheinungsjahr
- 2003
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- To evaluate whether beta-catenin signaling has a role in the regulation of angiogenesis in colon cancer, a series of angiogenesis-related gene promoters was analyzed for beta-catenin/TCF binding sites. Strikingly, the gene promoter of human vascular endothelial growth factor (VEGF, or VEGF-A) contains seven consensus binding sites for beta-catenin/TCF. Analysis of laser capture microdissected human colon cancer tissue indicated a direct correlation between up-regulation of VEGF-A expression and adenomatous polyposis coli (APC) mutational status (activation of beta-catenin signaling) in primary tumors. In metastases, this correlation was not observed. Analysis by immunohistochemistry of intestinal polyps in mice heterozygous for the multiple intestinal neoplasia gene (Min/+) at 5 months revealed an increase and redistribution of VEGF-A in proximity to those cells expressing nuclear beta-catenin with a corresponding increase in vessel density. Transfection of normal colon epithelial cells with activated beta-catenin up-regulated levels of VEGF-A mRNA and protein by 250-300%. When colon cancer cells with elevated beta-catenin levels were treated with beta-catenin antisense oligodeoxynucleotides, VEGF-A expression was reduced by more than 50%. Taken together, our observations indicate a close link between beta-catenin signaling and the regulation of VEGF-A expression in colon cancer.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0008-5472eISSN: 1538-7445Titel-ID: cdi_proquest_miscellaneous_73363796
- Format
- –
- Schlagworte
- Adenocarcinoma - blood supply, Adenocarcinoma - etiology, Adenocarcinoma - genetics, Adenocarcinoma - metabolism, Adenocarcinoma - pathology, Adenomatous Polyposis Coli - genetics, Adenomatous Polyposis Coli - metabolism, Animals, b-catenin, beta Catenin, Binding Sites, Biological and medical sciences, Colon - metabolism, Colonic Neoplasms - blood supply, Colonic Neoplasms - etiology, Colonic Neoplasms - genetics, Colonic Neoplasms - metabolism, Colonic Neoplasms - pathology, Cytoskeletal Proteins - genetics, Cytoskeletal Proteins - physiology, Dissemination, Endothelial Growth Factors - biosynthesis, Endothelial Growth Factors - genetics, Fibroblast Growth Factor 2 - analysis, Gene Expression Regulation, Neoplastic - drug effects, Gene Expression Regulation, Neoplastic - physiology, Genes, APC, Genes, ras, Growth Substances - genetics, Humans, Intercellular Signaling Peptides and Proteins - biosynthesis, Intercellular Signaling Peptides and Proteins - genetics, Intestinal Mucosa - metabolism, Lymphokines - biosynthesis, Lymphokines - genetics, Medical sciences, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Neoplasm Proteins - biosynthesis, Neoplasm Proteins - genetics, Oligodeoxyribonucleotides, Antisense - pharmacology, Promoter Regions, Genetic - genetics, Recombinant Fusion Proteins - physiology, RNA, Messenger - biosynthesis, RNA, Messenger - genetics, RNA, Neoplasm - biosynthesis, RNA, Neoplasm - genetics, Signal Transduction, Subcellular Fractions - chemistry, Trans-Activators - genetics, Trans-Activators - physiology, Transfection, Tumor cell, Tumor Cells, Cultured - drug effects, Tumor Cells, Cultured - metabolism, Tumors, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors