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Results for “oncogenic factor”

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At least 37 records · Page 2Linked to original sources
PubMed1999

EBV infection induced transformation of benign T lymphoproliferative state in patient with chronic active EBV infection into malignant lymphoma: implication of EBV infection as additive oncogenic factor in tumorigenesis.

An 11-year-old girl with chronic EBV (Epstein-Barr virus) infection, who later developed malignant lymphoma in the lung, is reported. She had an increased number of V alpha2, V beta8, CD3, CD4, and HLADR positive activated lymphocytes (20-30% of total lymphocytes) in peripheral blood. One year later, she developed lymphoma in the lung, which was V alpha2, V beta8, CD3, CD4, HLADR and IL2Rbeta positive. At that time, the population in the peripheral blood increased up to 40%, but there was no evidence of lymphoma in the bone marrow. In situ hybridization revealed lymphoma cells were EBER-1 positive but gp350/220 and LMP mRNA negative. The EBV genome was detected in the tumor, but not in the peripheral T cells. Clonal analysis of the lymphoma cells revealed monoclonal rearrangement of the TcRbeta and gamma gene, however, investigation of the terminal repeat of EBV gene did not show the monoclonal pattern. These results indicate that infection of EBV into clonally activated T cells was related with transformation from benign lymphoproliferative disease to malignant lymphoma in this patient.

Child↗
PubMed2003

Biallelic transcriptional activation of oncogenic transcription factors in T-cell acute lymphoblastic leukemia.

Aberrant expression of transcription factor oncogenes such as HOX11, HOX11L2, TAL1/SCL, LYL1, LMO1, and LMO2 can be detected in lymphoblasts from up to 80% of patients with acute T-cell lymphoblastic leukemia (T-ALL). Transcriptional activation of these oncogenes in leukemic cells typically results from chromosomal rearrangements that place them next to highly active cis-acting transcriptional regulatory elements. However, biallelic activation of TAL1 in some T-ALL cases has been previously proposed. We have used allele-specific mRNA analysis to show that trans-acting mechanisms leading to biallelic overexpression of TAL1 are involved in 10 (42%) of 24 TAL1+ informative T-ALL cases, 2 (17%) of 12 HOX11+ informative cases, and 7 (64%) of 11 LMO2+ informative cases. We propose that aberrant expression of oncogenic transcription factors in a significant fraction of T-ALLs may result from loss of the upstream transcriptional mechanisms that normally down-regulate the expression of these oncogenes during T-cell development.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Identification and characterization of nucleophosmin/B23/numatrin which binds the anti-oncogenic transcription factor IRF-1 and manifests oncogenic activity.

Interferon regulatory factor-1 (IRF-1) acts as a transcriptional activator in the interferon system and as a tumor suppressor. The loss of functional IRF-1 has been observed in a significant number of patients with myelodysplastic syndrome (MDS) and leukemia, suggesting a potentially critical role of IRF-1 in human oncostasis. Here we report an alternative mechanism by which IRF-1 may be inactivated. We purified an IRF-1 association molecule which was revealed to be identical to a nuclear factor nucleophosmin (NPM)/B23/numatrin. Functional analysis showed that NPM inhibited the DNA-binding and transcriptional activity of IRF-1. Moreover, NPM was overexpressed in several clinical leukemia samples and human-derived leukemia cell lines. Finally, overexpression of NPM in NIH3T3 cells resulted in malignant transformation. These results suggest the possible involvement of NPM in inactivating IRF-1-dependent anti-oncogenic surveillance in human cancer development.

3T3 Cells↗
PubMed2004

[Oncogenic transcription factors as splicing regulators].

Oncogene activity ranges from transduction signals to transcription factors. Altered expression of oncogenes, either by chromosomal translocation, proviral insertion or point mutations, can lead to tumor formation. More specifically, data accumulated through the last two decades have shown that disregulation of oncogenic transcription factors can interfere with regulatory cascades that control the growth, differentiation, and survival of normal cells. There is also evidence that alterations of oncogene activity are associated with pre-mRNA splicing defects. The insights gained from the pivotal role of RNA polymerase II in coupling transcription and splicing have instigated a new line of research regarding the possible role of oncogenic transcription factors in pre-mRNA splicing regulation. This review focuses on recent advances addressing this question. Understanding the impact of alterations in the expression and/or function of oncogenes have important prognostic implications that can guide the design of new therapeutic drugs to promote differentiation and/or apoptosis over cell proliferation.

Apoptosis↗
PubMed1997

Phosphorylation of the oncogenic transcription factor interferon regulatory factor 2 (IRF2) in vitro and in vivo.

IRF2 is a transcription factor, possessing oncogenic potential, responsible for both the repression of growth-inhibiting genes (interferon) and the activation of cell cycle-regulated genes (histone H4). Surprisingly little is known about the post-translational modification of this factor. In this study, we analyze the phosphorylation of IRF2 both in vivo and in vitro. Immunoprecipitation of HA-tagged IRF2 expressed in 32P-phosphate labelled COS-7 cells demonstrates that IRF2 is phosphorylated in vivo. Amino acid sequence analysis reveals that several potential phosphorylation sites exist for a variety of serine/threonine protein kinases, including those of the mitogen activated protein (MAP) kinase family. Using a battery of these protein kinases we show that recombinant IRF2 is a substrate for protein kinase A (PKA), protein kinase C (PKC), and casein kinase II (CK2) in vitro. However, other serine/threonine protein kinases, including the MAP kinases JNK1, p38, and ERK2, do not phosphorylate IRF2. Two-dimensional phosphopeptide mapping of the sites phosphorylated by PKA, PKC, and CKII in vitro demonstrates that these enzymes are capable of phosphorylating IRF2 at multiple distinct sites. Phosphoaminoacid analysis of HA-tagged IRF2 immunoprecipitated from an asynchronous population of proliferating, metabolically phosphate-labelled cells indicates that this protein is phosphorylated exclusively upon serine residues in vivo. These results suggest that the oncogenic protein IRF2 may be regulated via multiple pathways during cellular growth.

Animals↗
PubMed1995

Oncogenic osteomalacia: evidence for a humoral phosphaturic factor.

Oncogenic osteomalacia is a syndrome characterized by phosphaturia, hypophosphatemia, reduced vitamin D levels, and osteomalacia. The cause is not known, but all patients have had a tumor; usually of mesenchymal origin. Removal of the tumor reverses the metabolic abnormalities. We report a patient with osteomalacia, severe hypophosphatemia, elevated alkaline phosphatase, low 1,25-dihydroxyvitamin D3, and phosphaturia. A tumor was identified in the infratemporal fossa. The tumor was removed, and all of the biochemical abnormalities resolved over the subsequent 8 months. The bone density returned to normal values. The tumor had the appearance of a paraganglioma and was used to establish a cell culture line called JH-55. Electron microscopy of the original tumor and the JH-55 cells demonstrated the presence of neurosecretory granules. A bioassay using opossum kidney cells was used to evaluate phosphate transport. Conditioned medium from the JH-55 cells inhibited phosphate reabsorption by the kidney tubular cells. Maximal inhibition required a 24-h incubation period and was not altered by the presence of an inhibitor of protein synthesis (10 micrograms/mL cycloheximide). Immunoassays revealed no detectable PTH-related peptide or intact PTH in the JH-55 medium. The cause of this paraneoplastic syndrome is not known, but all of the evidence is consistent with the action of a hormone that produces phosphaturia. This putative factor is distinct from other hormones that cause phosphaturia.

Animals↗
PubMed2006

Identification of a chemical inhibitor of the oncogenic transcription factor forkhead box M1.

The oncogenic transcription factor forkhead box M1 (FoxM1) is overexpressed in a number of different carcinomas, whereas its expression is turned off in terminally differentiated cells. For this reason, FoxM1 is an attractive target for therapeutic intervention in cancer treatment. As a first step toward realizing this goal, in this study, using a high-throughput, cell-based assay system, we screened for and isolated the antibiotic thiazole compound Siomycin A as an inhibitor of FoxM1. Interestingly, we observed that Siomycin A was able to down-regulate the transcriptional activity as well as the protein and mRNA abundance of FoxM1. Consequently, we found that the downstream target genes of FoxM1, such as Cdc25B, Survivin, and CENPB, were repressed. Also, we observed that consistent with earlier reports of FoxM1 inhibition, Siomycin A was able to reduce anchorage-independent growth of cells in soft agar. Furthermore, we found that Siomycin A was able to induce apoptosis selectively in transformed but not normal cells of the same origin. Taken together, our data suggest that FoxM1 inhibitor Siomycin A could represent a useful starting point for the development of anticancer therapeutics.

Animals↗
PubMed2000

Regulation of expression of the human beta-1,2-N-acetylglucosaminyltransferase II gene (MGAT2) by Ets transcription factors.

Oncogenic transformation of fibroblasts by the src oncogene has long been known to cause an increase in the size of cell-surface protein-bound oligosaccharides, owing primarily to increased N-glycan branching mediated by increased beta-1,6-N-acetylglucosaminyltransferase V (GnT V) activity. The src-responsive element of the GnT V promoter was localized to Ets-binding sites and the promoter was transcriptionally stimulated by both ets-1 and ets-2 expression [Buckhaults, Chen, Fregien and Pierce (1997) J. Biol. Chem. 272, 19575-19581; Kang, Saito, Ihara, Miyoshi, Koyama, Sheng and Taniguchi (1996) J. Biol. Chem. 271, 26706-26712]. Because GnT V action requires the prior action of beta-1,2-N-acetylglucosaminyltransferase II (GnT II) and the human GnT II promoter contains four putative Ets-binding sites [Chen, Zhou, Tan and Schachter (1998) Glycoconj. J. 15, 301-308], GnT II might also be under oncogenic control via Ets transcription factors. We now report that co-transfection into HepG2 or COS-1 cells of either ets-1 or ets-2 expression plasmids together with chimaeric GnT II promoter-chloramphenicol acetyltransferase plasmids results in a 2-4-fold stimulation of promoter activity. Mobility-shift assays and South-Western blots localized the functional Ets-binding site to one of the four putative sites on the GnT II promoter. The GnT II promoter, unlike the GnT V promoter, is not activated by either src or neu. Therefore although both promoters are stimulated by a member of the Ets family of transcription factors, the functional role of this Ets transcriptional control seems to be different for the two genes.

Animals↗
PubMed1985

Role of growth factors in oncogenesis: growth factor-proto-oncogene pathways of mitogenesis.

Cellular genes which encode proteins involved in the response of cells to stimulation by growth factors may be potential oncogenes. The factors involved in the signal transmission from growth factor-receptor interaction to DNA synthesis constitute a cascade system which we call the 'growth factor-proto-oncogene pathway(s) of mitogenesis'. For each growth factor, all the responsive cells, regardless of cell types and tissue source, have specific growth factor receptors which are similar, if not identical, in molecular weight and biological activity. Thus, we believe that the growth factor-proto-oncogene pathway(s) functions in the same manner in all responsive cells. Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and brain-derived growth factor (BDGF) are major growth factors for connective tissue cells and do not share a common pathway in mitogenesis in responsive cells. The gene product of c-myc may be involved in the cellular response of cells stimulated by PDGF or FGF, but not directly in the signal transmission which leads to DNA synthesis.

Animals↗
PubMed1996

Growth factors and oncogene products in transitional cell carcinoma.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) stimulate cellular proliferation, whereas epidermal growth factor receptor (EGFR) and c-erb-B-2 oncoprotein are involved in the regulation of cellular growth. Although the immunoreactivity for growth factors and oncogene products in transitional cell carcinoma (TCC) of the urinary bladder has been shown to correlate with clinicopathologic findings and prognoses, there have been no such reports on TCC of the upper urinary tract (TCC-UUT). The present study investigated the prognostic value of these growth factors (EGF and TGF-alpha) and oncogene products (EGFR and c-erb-B-2) in TCC-UUT. Formalin-fixed, paraffin-embedded tumor tissues from 133 patients with TCC-UUT were analyzed using immunohistochemical staining. Immunohistochemically, EGF was recognized as positive in 50.4% of the samples, TGF-alpha in 27.8%, EGFR in 41.3%, and c-erb-B-2 oncoprotein in 6.8%. The immunoreactivity for EGF and c-erb-B-2 oncoprotein was significantly (P < 0.05) correlated with both stage and grade, whereas TGF-alpha correlated only with stage and EGFR only with grade. The 5-year survival rate for all cases taken together was 66.7%. Univariate analysis revealed that patients with EGF- and c-erb-B-2 oncoprotein-positive tumors had a worse clinical course than patients with EGF- and c-erb-B-2 oncoprotein-negative tumors, whereas in the final models of multivariate analysis, stage was found to be the only prognostic factor. Detection of immunoreactivity for growth factors and oncogene products does not appear to be of any real value in deciding the prognosis of TCC-UUT.

Adult↗