Search results for "Regulatory"
showing 10 items of 740 documents
The BCL6 gene in B-cell lymphomas with 3q27 translocations is expressed mainly from the rearranged allele irrespective of the partner gene
2003
The BCL6 gene, which functions as a transcription repressor, is the target of multiple chromosomal translocations in non-Hodgkin's lymphomas (NHL). These translocations occur in the nontranslated region of the BCL6 gene, juxtaposing regulatory sequences of the diverse partner genes to the open reading frame of the BCL6 gene and thus are thought to deregulate BCL6 gene expression. The levels of expression of the BCL6 gene and protein have been demonstrated to predict the clinical outcome of diffuse large B-cell lymphomas. By contrast, the prognostic significance of BCL6 gene translocations is unclear. In this study we have sought an explanation for this apparent discrepancy. We examined tumo…
Breast cancer genome-wide association studies: there is strength in numbers.
2012
Breast cancer (BC) is a heterogeneous disease that exhibits familial aggregation. Family linkage studies have identified high-penetrance genes, BRCA1, BRCA2, PTEN and TP53, that are responsible for inherited BC syndromes. Moreover, a combination of family-based and population-based approaches indicated that genes involved in DNA repair, such as CHEK2, ATM, BRIP and PALB2, are associated with moderate risk. Therefore, all of these known genes account for only 25% of the familial aggregation cases. Recently, genome wide association studies (GWAS) in BC revealed single nucleotide polymorphisms (SNPs) in five novel genes associated to susceptibility: TNRC9, FGFR2, MAP3K1, H19 and lymphocyte-spe…
Redistribution of CD95, DR4 and DR5 in rafts accounts for the synergistic toxicity of resveratrol and death receptor ligands in colon carcinoma cells.
2004
The natural phytoalexin resveratrol (3, 5, 4'-trihydroxystilbene) exhibits both chemopreventive and antitumor activities through a variety of mechanisms. We have shown previously that resveratrol-induced apoptosis of a human colon cancer cell line involved the redistribution of CD95 (Fas/Apo-1) into lipid rafts. Here, we show that, in colon cancer cells that resist to resveratrol-induced apoptosis, the polyphenol also induces a redistribution of death receptors into lipid rafts. This effect sensitizes these tumor cells to death receptor-mediated apoptosis. In resveratrol-treated cells, tumor necrosis factor (TNF), anti-CD95 antibodies and TNF-related apoptosis-inducing ligand (TRAIL) activa…
Altered Expression of c-IAP1, Survivin, and Smac Contributes to Chemotherapy Resistance in Thyroid Cancer Cells
2006
Abstract Resistance to chemotherapy predicts an unfavorable outcome for patients with radioiodine-insensitive thyroid cancer. To investigate the mechanisms underlying this resistance, we evaluated the expression of four different inhibitor of apoptosis proteins, and their antagonist, Smac, in thyroid cancer cells that survived 48 hours of exposure to cisplatin, doxorubicin, or taxol. We found high levels of c-IAP1 after cisplatin treatment and increased expression of survivin following exposure to doxorubicin. Cells that endured treatment with taxol showed reduced expression of Smac and released minimal amounts of this protein from the mitochondria. Down-regulation of c-IAP1 and survivin in…
Hsp72 controls bortezomib-induced HepG2 cell death via interaction with pro-apoptotic factors.
2007
The proteasome inhibitor bortezomib is an efficacious inducer of apoptosis in the hepatoma HepG2 cell line. This study shows that bortezomib increased in these cells the level of the survival factor Hsp72 in a time- and dose-dependent manner. In a first phase of treatment, Hsp72 rapidly increased so that at 24 h of incubation with 50 nM bortezomib its level was approximately five-fold higher than the control. In this phase Hsp72 seemed to play a role in preventing HepG2 cell death, since it interacted with and sequestered the pro-apoptotic factors p53, AIF, Bax and Apaf-1. During a second day of treatment, although the nuclear levels of Hsp72, p53 and AIF increased, the interaction of Hsp72…
Histone deacetylase inhibition by valproic acid down-regulates c-FLIP/CASH and sensitizes hepatoma cells towards CD95-and TRAIL receptor-mediated apo…
2005
Hepatocellular carcinoma (HCC) is highly resistant to chemotherapy, leading to a poor prognosis of advanced disease. Inhibitors of histone deacetylase (HDACi) induce re-differentiation in tumor cells and thereby re-establish sensitivity towards apoptotic stimuli. HDACi are entering the clinical stage of tumor treatment, and several substances are currently being tested in clinical trials to prove their efficacy in the treatment of leukemias and solid tumors. In this study, we investigated the impact of the HDACi valproic acid (VA) on TRAIL- and CD95-mediated apoptosis in hepatoma cells, as well as its sensitizing effect on a chemotherapeutic agent. Treatment of HepG2 cells with VA increased…
Targeting apoptosis proteins in hematological malignancies
2010
The apoptotic machinery plays a key role in hematopoietic cell homeostasis. Terminally differentiated cells are eliminated, at least in part, by apoptosis, whereas part of the apoptotic machinery, including one or several caspases, is required to go through very specific steps of the differentiation pathways. A number of hematological diseases involve a deregulation of this machinery, which in most cases is a decrease in cell sensitivity to pro-apoptotic signals through over-expression of anti-apoptotic molecules. In some situations however, e.g. in the erythroid lineage of low grade myelodysplastic syndromes, cell sensitivity to apoptosis is increased in a death receptor-dependent manner a…
Estrogen receptor α regulates non-canonical autophagy that provides stress resistance to neuroblastoma and breast cancer cells and involves BAG3 func…
2015
AbstractBreast cancer is a heterogeneous disease and approximately 70% of newly diagnosed breast cancers are estrogen receptor (ER) positive. Out of the two ER types, α and β, ERα is the only ER that is detectable by immunohistochemistry in breast cancer biopsies and is the predominant subtype expressed in breast tumor tissue. ER-positive tumors are currently treated with anti-hormone therapy to inhibit ER signaling. It is well known that breast cancer cells can develop endocrine resistance and resistance to anti-hormone therapy and this can be facilitated via the autophagy pathway, but so far the description of a detailed autophagy expression profile of ER-positive cancer cells is missing.…
Smac induces cytochrome c release and apoptosis independently from Bax/Bcl-xL in a strictly caspase-3-dependent manner in human carcinoma cells
2004
The mitochondrial apoptosis pathway mediates cell death through the release of various pro-apoptotic factors including cytochrome c and Smac, the second mitochondrial activator of caspases, into the cytosol. Smac was shown previously to inhibit IAP proteins and to facilitate initiation of the caspase cascade upon cytochrome c release. To investigate Smac function during apoptosis and to explore Smac as an experimental cancer therapeutic, we constructed an expression system based on a single adenoviral vector containing Smac under control of the Tet-off system supplied in cis. Conditional expression of Smac induced apoptosis in human HCT116 and DU145 carcinoma cells regardless of the loss of…
ERBB2 Induces an Antiapoptotic Expression Pattern of Bcl-2 Family Members in Node-Negative Breast Cancer
2010
AbstractPurpose: Members of the Bcl-2 family act as master regulators of mitochondrial homeostasis and apoptosis. We analyzed whether ERBB2 influences the prognosis of breast cancer by influencing the proapoptotic versus antiapoptotic balance of Bcl-2 family members.Experimental Design: ERBB2-regulated Bcl-2 family members were identified by inducible expression of ERBB2 in MCF-7 breast cancer cells and by correlation analysis with ERBB2 expression in breast carcinomas. The prognostic relevance of ERBB2-regulated and all additional Bcl-2 family members was determined in 782 patients with untreated node-negative breast cancer. The biological relevance of ERBB2-induced inhibition of apoptosis…