Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The t(11;22)(q24;q12) translocation is found in about 85% of Ewing tumors and leads in all cases to an EWS/FLI1 fusion gene. In a few instances, complex translocations, involving chromosomes 11, 22 and a third chromosome or other variant translocations not involving chromosome 11 also have been reported. These rearrangements generate an active fusion gene between the EWS gene and either the human FLI1 gene or other members of the ETS gene family: the ERG gene localized in band 21q22.2, the ETV1 gene localized in band 7p22, or the E1AF gene localized in band 17q12. Using fluorescence in situ hybridization (FISH) on interphase nuclei or metaphases, we report here the characterization of particular karyotypes in Ewing tumors, namely a complex t(2;11;22) translocation, a variant t(12;22) translocation, and one Ewing tumor without specific rearrangements but with an EWS/ERG fusion gene demonstrated by molecular analysis. These molecular cytogenetic methods allowed us (1) to precisely localize the genomic breakpoints within-EWSR1 and EWSR2 and to identify the chromosome carrying the fusion gene; (2) to determine the nature of events generating the fusion genes; (3) to demonstrate that some variant translocations represent masked complex translocations; and (4) to show that the generation of an EWS/ERG fusion gene cannot be obtained through a simple balanced translocation.
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PMID:Multiple chromosomal mechanisms generate an EWS/FLI1 or an EWS/ERG fusion gene in Ewing tumors. 924 12

There has been an explosion of new knowledge regarding the Ewing family of tumors over the past 5 to 10 years. Classical Ewing's sarcoma and PNET are now known to be the same tumor with variable differentiation, defined by a translocation between the EWS gene on chromosome 22 with one of three ETS-like genes, especially the FLI-1 gene on chromosome 11. Molecular techniques used to identify this translocation along with the knowledge that the protein product of the MIC2 gene is highly expressed on the cell surface have greatly improved our diagnostic abilities in this family of tumors. Controversy still exists as to whether surgery improves event-free survival when compared with radiotherapy in Ewing's sarcoma. The high second tumor rate, if nothing else, has started moving many physicians to preferentially use surgery when the functional results are predicted to be reasonable. The addition of ifosfamide and etoposide to standard therapy in Ewing's sarcoma has improved survival for patients without metastases at presentation. However, outcome for patients with metastases or who develop metastases while on therapy or shortly thereafter remains poor. Preliminary reports of better outcome with megatherapy are interesting but not yet definitive. The decades ahead will probably see marked changes in therapy for Ewing's sarcoma. The unique translocation seen in virtually all of these tumors is a potential target for a "magic bullet" therapy, because the protein product of this translocation is present only in the malignant cells. Hopefully either immune modulation against this unique protein or further knowledge of how to use antisense genes will move us toward exquisitely targeted therapy in the Ewing family of tumors.
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PMID:The Ewing family of tumors. Ewing's sarcoma and primitive neuroectodermal tumors. 928 96

HER2/Neu is overexpressed in 25-30% of all human breast cancers as a result of both gene amplification and enhanced transcription. Transcriptional upregulation of HER2/neu leads to a 6-8-fold increased abundance of its mRNA per gene copy and likely results from the elevated activity of transcription factors acting on the HER2/neu promoter. Here we report that transcripts of PEA3, an ETS transcription factor implicated in oncogenesis, were increased in 93% of HER2/Neu-overexpressing human breast tumor samples. Analyses to uncover the molecular basis for elevated PEA3 transcripts in HER2/Neu-positive breast tumors revealed that the HER2/Neu receptor tyrosine kinase initiated an intracellular signaling cascade resulting in increased PEA3 transcriptional activity; transcriptionally-activated PEA3 stimulated HER2/neu and PEA3 gene transcription by binding to sites in the promoters of these genes. PEA3 also activates transcription of genes encoding matrix-degrading proteinases, enzymes required for tumor cell migration and invasion. These findings implicate PEA3 in the initiation and progression of HER2/Neu positive breast cancer, and suggest that PEA3 and signaling proteins affecting its regulation are appropriate therapeutic targets.
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PMID:HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer. 938 Apr 3

The present study was undertaken to analyze the radiologic findings of intratemporal and extratemporal schwannoma (ITS & ETS). We retrospectively reviewed the CT (9 cases), MR (3 cases) and medical records of 10 facial schwannoma patients. After classifying these into ITS and ETS, radiologic and clinical findings were analyzed. The most common clinical manifestations were facial nerve dysfunction (6/6 cases, 100%) and hearing impairment (5/6 cases, 83.3%) in ITS and parotid mass (4/4 cases, 100%) in ETS. Geniculate ganglion (GG) was the most commonly involved segment of ITS (5/6 cases, 83.5%). On CT, ITS arising in GG (4 cases) showed erosion of the petrous bone (4 cases), cochlea (3 cases), lateral semicircular canal (1 case) and ossicles (3 cases). ITS arising in the mastoid segment (1 case) showed the destruction of the jugular plate and external auditory canal wall. All three ITS in which MRI was performed showed iso- to hypointensity on T1WI, hyperintensity on T2WI and well-enhanced on post-enhanced T1WI. ETS showed various findings, but all four ETS were located in the posterolateral portion of the retromandibular vein and extended toward the stylomastoid foramen. In conclusion, ITS shows the schwannoma on MR. ETS shows various findings. However, if the tumor is located along the extratemporal facial nerve course, then facial schwannoma may be suspected.
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PMID:Facial nerve schwannomas: CT and MR findings. 958 55

The Ewing tumor family of peripheral primitive neuroectodermal tumors (pPNETs) are characterized by chromosomal translocations leading to EWS-ETS gene fusions. These hybrid genes express chimeric proteins that are thought to act as aberrant transcription factors. We therefore used differential display-PCR to compare gene expression patterns in pPNET cell lines with those of other small round cell tumors (SRCTs) of childhood. This technique detected differential expression of sequences corresponding to human gastrin-releasing peptide (GRP) in pPNET cell lines but not in other SRCT cell lines. Subsequent Northern and reverse transcription-PCR analysis of SRCT cell lines confirmed GRP positivity in all pPNET lines tested. Of primary tumors tested by reverse transcription-PCR, GRP expression was found in 7 (44%) of 16 pPNETs but in no other primary SRCTs examined. Expression of the GRP receptor gene was demonstrable in 55% of pPNET cell lines and 25% of primary pPNET tumors but also in several other SRCTs. Radioimmunoassays and immunohistochemistry confirmed expression of bioactive GRP peptide in pPNET cell lines and primary tumors, respectively. Moreover, in vitro growth of a pPNET cell line was slowed by treatment with a GRP receptor antagonist and accelerated by a GRP receptor agonist. GRP is a known autocrine growth factor in small cell lung cancer and other neuroendocrine tumors. Its expression in pPNETs provides further evidence for a neuroectodermal histogenesis of these tumors and suggests that autocrine growth of this family of tumors may be at least partially regulated by GRP.
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PMID:The Ewing tumor family of peripheral primitive neuroectodermal tumors expresses human gastrin-releasing peptide. 962 91

Male and female strain A/J mice were exposed to environmental tobacco smoke that was generated by burning Kentucky 1R4F reference cigarettes. Exposures lasted 6 hours per day, 5 days per week for a total of 5 months, followed by a 4-month recovery period in air. Chamber concentrations of total suspended particulate matter (TSP) ranged from 50 to 90 mg/m3. Under these conditions, the average lung tumor multiplicity was 1.2 to 1.4 tumors per lung, significantly higher (p < 0.05) than in concomitant controls. ETS exposure led to a comparatively modest increase in cell proliferation in the alveolar zone during the first 2 weeks and in the terminal airways during the first 6 weeks. In the nasal passages cell proliferation was increased throughout, but reverted down to normal when the animals were placed in air. Smoke exposure increased immunostaining for cytochrome P4501A1 in airways and parenchyma. Exposure to the smoke gas phase only produced a similar increase in lung tumor multiplicity as did exposure to full smoke, but failed to induce P4501A1. This suggested that gas-phase constituents play an important role in tobacco smoke carcinogenesis. The strain A/J lung tumor model is thus suitable to study questions associated with tobacco smoke toxicity and carcinogenicity.
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PMID:Tobacco smoke as a mouse lung carcinogen. 965 72

To examine the relationship between exposure to passive smoke (herein referred to as environmental tobacco smoke, ETS), cooking fumes, other risk factors and primary adenocarcinoma of the lung, 70 adenocarcinoma lung cancer cases of non-smoking women in Nanjing were studied in a 1:1 case-control study. Results show no statistical association between exposure to ETS and pulmonary adenocarcinoma. The respective odds ratios for chronic lung disease, cooking fume pollution and family tumor history were 3.90, 2.45 and 4.36.
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PMID:Relation of exposure to environmental tobacco smoke and pulmonary adenocarcinoma in non-smoking women: a case control study in Nanjing. 968 39

Degradation of basement membranes and stromal extracellular matrix (ECM) is crucial for invasion and metastasis of malignant cells. Degradation of ECM is initiated by proteinases secreted by different cell types participating in tumor cell invasion, and increased expression or activity of every known class of proteinases (metallo-, serine-, aspartic-, and cysteine) has been linked to malignancy and invasion of tumor cells. Studies performed over the last decade have revealed that matrix metalloproteinases (MMPs) play a crucial role in tumor invasion. Expression of MMP genes is transcriptionally regulated by a variety of extracellular factors including cytokines, growth factors, and cell contact to ECM. This review will summarize the current view on the role of MMPs in tumor growth, invasion, and survival, and focus on the role of mitogen-activated protein kinases and AP-1 and ETS transcription factors in the regulation of MMP gene expression during invasion process.
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PMID:Regulation of matrix metalloproteinase expression in tumor invasion. 1022 22

Ewing's sarcoma (EWS) cells accumulate elevated steady-state levels of poly (ADP-ribose) polymerase (PARP) mRNA and protein. To understand the molecular mechanisms underlying PARP upregulation, we cloned and analysed the 5'-flanking region of the PARP gene from EWS cells. Nucleotide sequence analysis demonstrated no variations in the PARP promoter region in EWS cells. The PARP promoter encompasses multiple binding motifs for the ETS transcription factor. We have also observed that there is a coordinated up-regulation of the expression of both PARP and ETS1, relative to cells of other human tumor types expressing lower levels of PARP. Transient co-expression of ETS1 in EWS cells resulted in a strong enhancement of PARP-promoter activity. The participation of ETS in the regulation of PARP gene expression was further demonstrated in EWS cells stably transfected with Ets1 antisense cDNA constructs. Antisense-mediated down-regulation of endogenous ETS1 resulted in the inhibition of PARP expression in EWS cells, and sensitized these cells to ionizing radiation. These data provide support for ETS regulation of PARP expression levels, and implicate ETS transcription factors in the radiation response of EWS cells.
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PMID:Regulation of the human poly(ADP-ribose) polymerase promoter by the ETS transcription factor. 1043 18

Ets factors are members of an ancient multigene family of transcription factors including oncoproteins and possibly tumor suppressors. We previously characterized a novel divergent ets gene, Ehf (ets homologous factor) in mice. Here we report the cDNA sequence, chromosomal location, and tissue/tumor expression patterns of the human EHF gene and the regulatory activity of the EHF protein. EHF maps to 11p12, which is deleted in many prostate, breast, and lung carcinomas and is a hot spot for inherited deletion- or amplification-associated developmental defects. EHF is differentially expressed in normal tissues and carcinomas and between tumor stages and is most highly expressed in the organs known to form carcinomas upon 11p12 deletion. EHF protein represses the ETS-2 induced activity of both stromelysin-1 and collagenase-1 promoters. These data suggest that EHF may contribute to human development and carcinogenesis and is a candidate for the 11p12 tumor suppressor gene.
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PMID:Human chromosomal localization, tissue/tumor expression, and regulatory function of the ets family gene EHF. 1052 51


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