Search results for " Transcription factor"
showing 10 items of 656 documents
Nupr1-Aurora Kinase A Pathway Provides Protection against Metabolic Stress-Mediated Autophagic-Associated Cell Death
2012
Abstract Purpose: The limited supply of oxygen and nutrients is thought to result in rigorous selection of cells that will eventually form the tumor. Experimental Design: Nupr1 expression pattern was analyzed in human tissue microarray (TMA) and correlated with survival time of the patient. Microarray analysis was conducted on MiaPaCa2 cells subjected to metabolic stress in Nupr1-silenced conditions. DNA repair and cell cycle–associated gene expression was confirmed by real-time quantitative PCR (qRT-PCR). Nupr1 and AURKA protective role were analyzed using RNA interference (RNAi) silencing or overexpression. DNA damage and autophagy were analyzed by Western blot analysis and immunofluoresc…
JNK and AP-1 mediate apoptosis induced by bortezomib in HepG2 cells via FasL/caspase-8 and mitochondria-dependent pathways
2006
The proteasome inhibitor bortezomib is an efficacious apoptotic agent in many tumor cells. This paper shows that bortezomib induced apoptosis in human hepatoma HepG2 cells associated with many modifications in the expression of survival or death factors. Although bortezomib increased the level of the protective factors HSP70 and HSP27, the effects of the drug that favour cell death were predominant. These events include accumulation of c-Jun, phospho-c-Jun and p53; increase in FasL level with activation of caspase-8; changes related to members of Bcl-2 family with increase in the level of pro-apoptotic members and decrease in that of anti-apoptotic ones; dissipation of mitochondrial potenti…
Platelet-derived growth factor alpha mediates the proliferation of peripheral T-cell lymphoma cells via an autocrine regulatory pathway.
2014
Peripheral T-cell lymphomas not otherwise specified (PTCL/NOS) are very aggressive tumors characterized by consistent aberrant expression of platelet-derived growth factor receptor alpha (PDGFRA). In this study, we aimed to identify the determinants of PDGFRA activity in PTCL/NOS and to elucidate the biological consequences of its activation. We observed overexpression of the PDGFRA gene by gene expression profiling in most of the tested PTCLs and confirmed the expression of PDGFRA and phospho-PDGFRA using immunohistochemistry. The integrity of the PDFGRA locus was demonstrated using several different approaches, including massive parallel sequencing and Sanger sequencing. PDGF-AA was found…
Human FOXP3 and cancer.
2010
FOXP3 is a transcription factor necessary and sufficient for induction of the immunosuppressive functions in regulatory T lymphocytes. Its expression was first considered as specific of this cell type, but FOXP3 can also be transiently expressed in T-cell antigen receptor-activated human nonregulatory T cells. Recent data indicate that FOXP3 is also expressed by some nonlymphoid cells, in which it can repress various oncogenes that are restored following FOXP3 deletion or mutation. This review summarizes major advances in (1) the understanding of Foxp3 functions in human regulatory T cells, (2) the prognostic significance of Foxp3-expressing T cells in human malignancies and (3) the signifi…
pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 multimolecular complexes mediate the transcription of estrogen receptor-…
2003
The estrogen receptor-alpha (ER) plays a crucial role in normal breast development and is also linked to development and progression of mammary carcinoma. The transcriptional repression of ER-alpha gene in breast cancer is an area of active investigation with potential clinical significance. However, the molecular mechanisms that regulate the ER-alpha gene expression are not fully understood. Here we show a new molecular mechanism of ER-alpha gene inactivation mediated by pRb2/p130 in ER-negative breast cancer cells. We investigated in vivo occupancy of ER-alpha promoter by pRb2/p130-E2F4/5-HDAC1-SUV39 H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 complexes, and provided a link between p…
Do not stress, just differentiate: role of stress proteins in hematopoiesis
2015
Hematopoiesis permits the constant regeneration of the blood system and is a permanent example of cell differentiation. Defects in its tight regulation can lead to either cell death or abnormal proliferation and may translate into multiple types of blood disorders, including leukemia. Heat shock proteins (HSPs), the expression of which is controlled by heat shock factors (HSFs, currently four known members),1 are a set of highly conserved proteins induced in response to a wide variety of physiological and environmental stress. HSP/HSF overexpression or mislocalization has been described in many cancers, particularly in hematology, and other diseases. Therefore, the involvement of HSFs/HSPs …
Autocrine production of interleukin-4 and interleukin-10 is required for survival and growth of thyroid cancer cells.
2006
AbstractAlthough CD95 and its ligand are expressed in thyroid cancer, the tumor cell mass does not seem to be affected by such expression. We have recently shown that thyroid carcinomas produce interleukin (IL)-4 and IL-10, which promote resistance to chemotherapy through the up-regulation of Bcl-xL. Here, we show that freshly purified thyroid cancer cells were completely refractory to CD95-induced apoptosis despite the consistent expression of Fas-associated death domain and caspase-8. The analysis of potential molecules able to prevent caspase-8 activation in thyroid cancer cells revealed a remarkable up-regulation of cellular FLIPL (cFLIPL) and PED/PEA-15, two antiapoptotic proteins whos…
FOXP2 gene and language impairment in schizophrenia: association and epigenetic studies
2010
Abstract Background Schizophrenia is considered a language related human specific disease. Previous studies have reported evidence of positive selection for schizophrenia-associated genes specific to the human lineage. FOXP2 shows two important features as a convincing candidate gene for schizophrenia vulnerability: FOXP2 is the first gene related to a language disorder, and it has been subject to positive selection in the human lineage. Methods Twenty-seven SNPs of FOXP2 were genotyped in a cohort of 293 patients with schizophrenia and 340 controls. We analyzed in particular the association with the poverty of speech and the intensity of auditory hallucinations. Potential expansion of thre…
Haem oxygenase-1 induction reverses the actions of interleukin-1β on hypoxia-inducible transcription factors and human chondrocyte metabolism in hypo…
2013
HO-1 (haem oxygenase-1) catalyses the degradation of haem and possesses anti-inflammatory and cytoprotective properties. The role of inflammatory mediators in the pathogenesis of OA (osteoarthritis) is becoming increasingly appreciated. In the present study, we investigated the effects of HO-1 induction in OA and healthy HACs (human articular chondrocytes) in response to inflammatory cytokine IL-1 β (interleukin-1β) under hypoxic conditions. Hypoxia was investigated as it is a more physiological condition of the avascular cartilage. Hypoxic signalling is mediated by HIFs (hypoxia-inducible factors), of which there are two main isoforms, HIF-1α and HIF-2α. Normal and OA chondrocytes were sti…
Nuclear receptors modulate the interaction of Sp1 and GC-rich DNA via ternary complex formation
2000
Binding sites for transcription factor Sp1have been implicated in the transcriptional regulation of several genes by hormones or vitamins, and here we show that a GC-rich element contributes to the retinoic acid response of the interleukin 1β promoter. To explain such observations, it has been proposed that nuclear receptors can interact with Sp1 bound to GC-rich DNA. However, evidence supporting this model has remained indirect. So far, nuclear receptors have not been detected in a complex with Sp1 and GC-rich DNA, and the expected ternary complexes in non-denaturing gels were not seen. In search for these missing links we found that nuclear receptors [retinoic acid receptor (RAR), thyroid…