Abstract: The present application refers to methods for cancer diagnosis and treatment, particularly in types of cancers associated with aberrant CpG methylation of the miR-34a promoter.

Abstract: The present application refers to methods for cancer diagnosis and treatment, particularly in types of cancers associated with aberrant CpG methylation of the miR-34a promoter.

Abstract: The present invention relates to method and kits for diagnosing and/or treating prostate cancer. The method and kit relate to the determination and/or modulation of the methylation degree of tumor suppressive genes in biological samples. More particularly, CpG-methylation of 14-3-3? was found in all primary PCa samples analysed, but not in matching normal prostate epithelial cells or benign prostate hyperplasia (BPH). CpG-methylation was accompanied by a decrease or loss of 14-3-3? protein expression in primary PCa and PCa cell lines. PCa-precursor lesions, known as prostatic intraepithelial neoplasia (PIN), also displayed decreased levels of 14-3-3? expression, whereas normal prostate epithelial cells and BPH showed high levels of 14-3-3? protein expression. The generality of CpG-methylation in PCa suggests that silencing of 14-3-3? significantly contributes to the formation of PCa. Furthermore, the CpG-methylation of 14-3-3? in PCa may be exploited for diagnostic purposes.

Abstract: Exposure of colorectal cancer (CRC) cells to ionizing radiation results in a growth arrest, with cells blocked in both the G1 and G2 phases of the cell cycle. The G1 block has been shown to be due to the p53-mediated induction of the cyclin-dependent kinase inhibitor p21WAF1/CIP1/SDI1, but the basis for the G2 arrest is unknown. Through a quantitative analysis of gene expression patterns in CRC cell lines, we have discovered that 14-3-3&sgr; is strongly induced by &ggr;-irradiation and other DNA-damaging agents. The induction of 14-3-3&sgr; is mediated by a p53-responsive element located 1.815 kb upstream of its transcription start site. Exogenous introduction of 14-3-3&sgr; into cycling cells results in a G2 block similar to that observed following irradiation. These results document a molecular mechanism for G2/M control that is regulated in human cells by p53.

Abstract: The prototypic oncogene c-MYC encodes a transcription factor, which can drive proliferation by promoting cell cycle re-entry. However, the mechanisms through which c-MYC achieves these effects have been unclear. Using serial analysis of gene expression (SAGE), we have identified the cyclin dependent kinase 4 (CDK4) gene as a transcriptional target of c-MYC. c-MYC induced a rapid increase in CDK4 mRNA levels through four highly conserved c-Myc binding sites (MBS) within the CDK4 promoter. Cell cycle progression is delayed in c-MYC-deficient RAT1 cells, and this delay was associated with a defect in CDK4 induction. Ectopic expression of CDK4 in these cells partially alleviated the growth defect. Thus, CDK4 provides a direct link between the oncogenic effects of c-MYC and cell cycle regulation.

Abstract: Exposure of colorectal cancer (CRC) cells to ionizing radiation results in a growth arrest, with cells blocked in both the G1 and G2 phases of the cell cycle. The G1 block has been shown to be due to the p53-mediated induction of the cyclin-dependent kinase inhibitor p21WAF1/CIP1/SDI1, but the basis for the G2 arrest is unknown. Through a quantitative analysis of gene expression patterns in CRC cell lines, we have discovered that 14-3-3&sgr; is strongly induced by &ggr;-irradiation and other DNA-damaging agents. The induction of 14-3-3&sgr; is mediated by a p53-responsive element located 1.815 kb upstream of its transcription start site. Exogenous introduction of 14-3-3&sgr; into cycling cells results in a G2 block similar to that observed following irradiation. These results document a molecular mechanism for G2/M control that is regulated in human cells by p53.

Abstract: Exposure of colorectal cancer (CRC) cells to ionizing radiation results in a growth arrest, with cells blocked in both the G1 and G2 phases of the cell cycle. The G1 block has been shown to be due to the p53-mediated induction of the cyclin-dependent kinase inhibitor p21WAF1/CIP1/SDI1, but the basis for the G2 arrest is unknown. Through a quantitative analysis of gene expression patterns in CRC cell lines, we have discovered that 14-3-3&sgr; is strongly induced by &ggr;-irradiation and other DNA-damaging agents. The induction of 14-3-3&sgr; is mediated by a p53-responsive element located 1.815 kb upstream of its transcription start site. Exogenous introduction of 14-3-3&sgr; into cycling cells results in a G2 block similar to that observed following irradiation. These results document a molecular mechanism for G2/M control that is regulated in human cells by p53.