Furthermore, Bmi-1 and Cyclin D2 were found to be positively regulated by USP22, which may have mediated the tumorigenic effects of USP22 in human colon cancer.
These findings demonstrate that TTP acts as a negative regulator of VEGF gene expression in colon cancer cells, suggesting that it can be used as novel therapeutic agent to treat colon cancer.
Comparison of the transcriptome data of metastasis-competent CTC-MCC-41 cells and of HT-29 cells (derived from a primary colon cancer) highlights the differential expression of genes that regulate energy metabolism [peroxisome proliferator-activated receptor γ coactivator 1A (<i>PPARGC1A</i>), peroxisome proliferator-activated receptor γ coactivator 1B (<i>PPARGC1B</i>), fatty acid binding protein 1 (<i>FABP1</i>), aldehyde dehydrogenase 3 family member A1 (<i>ALDH3A1</i>)], DNA repair [BRCA1 interacting protein C-terminal helicase 1 (<i>BRIP1</i>), Fanconi anemia complementation group B (<i>FANCB</i>), Fanconi anemia complementation group M (<i>FANCM</i>)], and stemness [glutaminase 2 (<i>GLS2</i>), cystathionine-beta-synthase (<i>CBS</i>), and cystathionine gamma-lyase (<i>CTH</i>)].
To analyze the biological activities of these VEGF isoforms on tumor growth, we transfected human VEGF121, VEGF165 or VEGF189 cDNA into the human colon cancer cell line SW-480, and established several clones overexpressing these VEGF isoforms.
These studies demonstrate that the IGF ligand-receptor system plays an important role in multiple mechanisms that mediate human colon cancer growth including regulation of VEGF and angiogenesis.
1,1-Bis(3'-indolyl)-1-(p-substitutedphenyl)methanes are peroxisome proliferator-activated receptor gamma agonists but decrease HCT-116 colon cancer cell survival through receptor-independent activation of early growth response-1 and nonsteroidal anti-inflammatory drug-activated gene-1.
We also correlated EZR and PPARγ expression in our series of CRC specimens and the expression profiling of all five proteins levels in the publicly available colon cancer genomic data from Oncomine and Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) datasets.
Although the VEGF -2578C > A polymorphism had no influence on susceptibility to colon cancer, some genotypes showed a significant difference between the case and control groups when the data were stratified by gender and the original location of tumor, suggesting that the VEGF -2578C > A polymorphism, at least in Koreans, is a genetic determinant of colon cancer risk.
These factors could allow neoplastic tissues to survive and withstand the stress induced by hypoxia and/or disruption of the ECM, including vascular endothelial growth factor and matrix metalloproteinases that were found to be highly elevated in tumor tissues of colon cancer patients.
IHC studies performed on human colon adenocarcinoma specimens showed that TGF-beta signaling is inversely correlated with VEGFA expression, indicating that TGF-beta-mediated suppression of VEGFA expression exists in colon cancer patients.
Other studies have suggested an inverse relationship between p53 and bcl-2 protein expression in breast and colonic cancers and in a variety of subtypes of non-Hodgkin's lymphoma.
After stratifying by tumor molecular subtype, SNP associations observed for colon cancer were: VEGFArs2010963 with CIMP+ colon tumors; FLT1 rs4771249 and rs7987649 with TP53; FLT1 rs3751397, rs7337610, rs7987649, and rs9513008 and KDR rs10020464, rs11941492, and rs12498529 with MSI+ and CIMP+/KRAS2-mutated tumors.
A stable VEGF gene-transfected human colon cancer cell line, LoVo, was made by genetic manipulation using eukaryotic expression constructs designed to express the complete VEGF121 cDNA in the sense orientation.
Stratified meta-analysis indicated that PPAR-gamma 34 C>G was associated with colon cancer (OR = 0.8, 95% CI: 0.65-0.99, P = 0.04) in random-effect model, and the G allele decreased colon cancer risk.
In vitro assessments were then made of the ability of anti-VEGF siRNA to knock down expression of VEGF and the subsequent effect this decreased expression had on colon cancer cell proliferation.