Protumorigenic effects of Snail-expression fibroblasts on colon cancer cells.

Snail1 is a transcriptional factor that plays an important role in epithelial-mesenchymal transition and in the acquisition of invasive properties by epithelial cells. In colon tumors, Snail1 expression in the stroma correlates with lower specific survival of cancer patients. However, the role(s) of Snail1 expression in stroma and its association with patients' survival have not been determined.

TWIST1 is expressed in colorectal carcinomas and predicts patient survival.

TWIST1 is a transcription factor that belongs to the family of basic helix-loop-helix proteins involved in epithelial-to-mesenchymal transition and invasion processes. The TWIST1 protein possesses oncogenic, drug-resistant, angiogenic and invasive properties, and has been related with several human tumors and other pathologies. Colorectal cancer is one of the tumors in which TWIST1 is over-expressed, but its involvement in the clinical outcome of the disease is still unclear.

Deregulated expression of miR-106a predicts survival in human colon cancer patients.

MicroRNAs (miRNAs) are noncoding RNAs that regulate expression of target mRNAs and are controlled by tumor suppressors and oncogenes. Altered expression of specific miRNAs in several tumor types and its association with poor prognosis parameters have been reported. Fewer data are available on its impact on patients' survival.

Prognostic value of LISCH7 mRNA in plasma and tumor of colon cancer patients.

Purpose: LISCH7 is a gene potentially regulated by p53 that is up-regulated in metastasis development. Our hypothesis was that the expression of LISCH7 in primary colorectal tumors determined certain characteristics of the tumors, as well as their behavior, and that its identification in plasma could serve as a prognostic marker.

Experimental Design: We tested this hypothesis in a series of 115 tumors and normal tissues and in 83 plasmas from patients with sporadic colorectal carcinomas, as well as in 20 healthy control plasmas in which the expression levels of the gene were measured by real-time PCR.

The expression levels of the transcriptional regulators p300 and CtBP modulate the correlations between SNAIL, ZEB1, E-cadherin and vitamin D receptor in human colon carcinomas.

ZEB1 and SNAIL repress CDH1 and induce epithelial-mesenchymal transition (EMT). However, SNAIL and ZEB1 also activate or regulate other target genes in different ways. For instance, vitamin D receptor (VDR), which activates CDH1 expression upon ligand binding, is repressed by SNAIL but induced by ZEB1.

Thymidylate synthase messenger RNA expression in plasma from patients with colon cancer: prognostic potential.

Purpose: Thymidylate synthase (TS), a critical target in fluorouracil-based chemotherapy, is a prognostic marker in colon carcinomas and a predictor of response to treatment. Tumor RNA has been detected in plasma from cancer patients and is associated with poor prognosis. This is the first study to examine extracellular TS mRNA in plasma from patients with colon carcinoma, and its possible relation with TS promoter enhancer region (TSER) polymorphism.

E-cadherin and vitamin D receptor regulation by SNAIL and ZEB1 in colon cancer: clinicopathological correlations.

E-cadherin (CDH1) gene expression is strictly regulated. The transcriptional factors SNAIL and ZEB1 are involved in its repression, whereas activation of vitamin D receptor (VDR) by vitamin D induces its transcription. We study the expression and functional correlation of SNAIL, CDH1, VDR and ZEB1 genes and examine their possible involvement in colon cancer.

The GADD45, ZBRK1 and BRCA1 pathway: quantitative analysis of mRNA expression in colon carcinomas.

GADD45 is a growth arrest-associated gene that is induced in response to DNA damage. This gene is a target for coordinate regulation by both ZBRK1 and BRCA1. A sequence within intron 3 of GADD45 supports specific assembly of the ZBRK1/BRCA1 complex.

Overexpression of p16INK4a correlates with high expression of p73 in breast carcinomas.

The p16-cyclin D-Cdk4(6)-pRB-E2F and p73 pathways are involved in the control of cell-cycle progression, and genetic lesions in both pathways frequently occur in breast carcinomas and other human cancers. The p16INK4a gene is involved in regulation of the G1/S transition, and when overexpressed, the p73 gene activates transcription of p53-responsive genes and promotes apoptosis. These pathways are related, for instance, p73 is also downstream of E2F-1, since E2F-1 induces p73-mediated apoptosis in the absence of p53.

The transcription factor SNAIL represses vitamin D receptor expression and responsiveness in human colon cancer.

Several non-hypercalcemic analogs of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3)) show antitumor activity in a subset of cancer patients. High vitamin D receptor (VDR) expression, which is associated with good prognosis but is lost during tumor progression. We show that the SNAIL transcription factor represses VDR gene expression in human colon cancer cells and blocks the antitumor action of EB1089, a 1,25(OH)(2)D(3) analog, in xenografted mice.

Promoter methylation of the PTEN gene is a common molecular change in breast cancer.

About 25-50% of women with Cowden disease, a syndrome associated with germ-line mutations of the PTEN gene (at 10q23), develop breast cancer (BC), but PTEN mutations have been found in only 5% of sporadic BCs. However, 29-48% of BCs display loss of heterozygosity in 10q23, and about 40% of BCs show a decrease or absence of PTEN protein levels at the time of diagnosis. Promoter hypermethylation has been identified as an alternative mechanism of tumor-suppressor gene inactivation, but its importance in PTEN silencing in sporadic BC is unknown.

Prevalence of aberrant methylation of p14ARF over p16INK4a in some human primary tumors.

The INK4a/ARF locus encodes two unrelated tumor suppressor proteins, p16INK4a and p14ARF, which participate in the two main cell-cycle control pathways, p16-Rb and p14-p53. Methylation of CpG promoter islands has been described as a mechanism of gene silencing. Exon 1 of the p16INK4a gene and the p14ARF promoter gene reside within CpG islands.

Intratumoral heterogeneity in microsatellite alterations in BRCA1 and PTEN regions in sporadic colorectal cancer.

Background: Chromosome regions 17q21 (BRCA1) and 10q23 (PTEN) have been found deleted in colorectal cancer.

Methods: We studied the frequency of loss of heterozygosity (LOH) in these 2 regions in 214 patients with only 1 sample per tumor and in 100 patients with several samples per tumor. Three microsatellite markers of each region were used for the LOH test.

Concomitant expression of p16INK4a and p14ARF in primary breast cancer and analysis of inactivation mechanisms.

The INK4a/ARF locus encodes two tumour suppressor proteins, p16INK4a and p14ARF, which act in the two main cell-cycle control pathways, p16-Rb and p14-p53 respectively. The present study examined the mRNA expression of these genes by reverse transcription-polymerase chain reaction (RT-PCR), and the inactivation mechanisms that alter these levels, in 100 primary breast carcinomas. Furthermore, the interdependence of these mechanisms was examined, since it has been reported that p14ARF is altered in most tumours in concordance with p16INK4a.