Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intense depolarizing stimuli induce the expression of the proto-oncogene c-fos which may be useful as a marker of neuronal activity. To determine if mild physical and behavioral stressors may also induce c-fos expression, we subjected rats to an unconditioned stressor (footshock) or a conditioned stressor (a tone previously paired with footshock) and measured c-fos mRNA levels in various brain regions using in situ hybridization. Removing rats from their home cage and exposing them to a tone was sufficient to cause increases in c-fos mRNA in several forebrain areas while further increases in c-fos occurred in the septum, cingulate cortex, and endopiriform nucleus in response to acute footshock stress. Both unconditioned and conditioned stressors increased c-fos mRNA levels in the locus ceruleus which correlated with stress-induced plasma corticosterone concentrations. Unconditioned footshock stress also increased c-fos mRNA in the hypothalamic paraventricular nucleus (PVN). However, neither conditioned nor unconditioned stressors induced c-fos in the PVN in rats which had been previously exposed to footshock. C-fos appears to be a sensitive marker for stress-responsive brain areas and may be important in mediating long-term neurochemical changes that result from stress.
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PMID:Induction of c-fos mRNA in rat brain by conditioned and unconditioned stressors. 151 Dec 71

There is increasing interest in cellular localization of protooncogene, growth factor, and growth factor receptor gene expression in developing or neoplastic human tissue. Establishment of nucleic acid in situ hybridization (ISH) and immunohistochemical (IH) analyses of these genes, however, is compromised by the paucity of available control tissues which have been shown to express these cancer associated genes. The present study evaluated whether proto-oncogene or growth factor gene expressing human control tissues suitable for ISH and IH studies could be produced from malignant cell lines implanted into irradiated nude mice. Tumors rapidly fixed in parafomaldehyde 2 to 4 weeks after xenograft were found optimal for in situ hybridization and immunohistochemistry. Northern blots of frozen tumors confirmed the expression of specific proto-oncogenes in the tissue and the specificity of cDNA and cRNA probes for those transcripts. Production of control tissue from xenografted cell lines should facilitate establishment and long term quality control of in situ hybridization and immunohistochemical analysis of proto-oncogene or growth factor gene expression in laboratories with limited experience in these techniques.
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PMID:Production of proto-oncogene expressing control tissues for in situ hybridization and immunohistochemical studies. 273 11

Although carcinogens cause various similar deleterious effects on rodent and human cells, only rodent cells can convert to malignancy in a quantitative, predictable fashion. Therefore, the control mechanisms involving indefinite proliferation and tumorigenicity are different. Human cell lines may exhibit normal or aneuploid chromosome constitutions with numerical or structural alterations frequently involving proto-oncogene loci, but fail to produce progressively growing tumors in nude mice. A new approach for obtaining human cells susceptible to malignant transformation by chemical or physical carcinogens is to use DNA from a cancer associated virus. Transfection of human papilloma virus (HPV) DNA associated with genital cancer can extend life-span of human cells; post-X-irradiated cells grow in agar suspension. Southern blot analysis of extracted DNA indicates that HPV sequences persist. Similar results are obtained with human fibroblast and epithelial cells.
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PMID:In vitro models for studying the molecular biology of carcinogenesis. 354 64

To discern the effects of hyperthermia on working memory, we recorded the ability of rats to discriminate between objects following microwave radiation exposure. Memory changes were evaluated by measuring relative exploration time of a familiar vs. a new stimulus object. A subject that extensively reexplores a stimulus with which it has previous experience is presumed to exhibit memory loss associated with that object. Between training and testing, rats were exposed to various doses of microwave radiation, were sham irradiated, or remained in their home cage. Brain (dural) and rectal temperatures were recorded. To discern brain regions activated or possibly damaged by microwave exposure, we also used immunocytochemistry techniques to identify sites of c-fos protein expression in the brains of several irradiated/sham-irradiated subjects. Rats exposed to > 5 W/kg exhibited hyperthermia when compared to nonirradiated controls. Normothermic control subjects (sham-irradiated rats and rats exposed to 0.1 W/kg) showed a distinct preference for the new object although other microwave-exposed rats (1, 5, 8.5, 9.3, 10 W/kg) did not. Microwave hyperthermia evoked prominent c-fos expression in periventricular strata, hypothalamic nuclei, amygdala, and several areas of the cortex. These data suggest that performance on a putative working memory task may be disrupted by a sufficiently intense microwave-induced hyperthermia. The pattern of expression of the early proto-oncogene c-fos may suggest candidate brain nuclei that mediate the behavioral changes we observed.
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PMID:Disruption of a putative working memory task and selective expression of brain c-fos following microwave-induced hyperthermia. 804 68

The human proto-oncogene c-myc encodes a highly unstable transcription factor that promotes cell proliferation. Although the extreme instability of Myc plays an important role in preventing its accumulation in normal cells, little is known about how Myc is targeted for rapid destruction. Here, we have investigated mechanisms regulating the stability of Myc. We show that Myc is destroyed by ubiquitin-mediated proteolysis, and define two elements in Myc that oppositely regulate its stability: a transcriptional activation domain that promotes Myc destruction, and a region required for association with the POZ domain protein Miz-1 that stabilizes Myc. We also show that Myc is stabilized by cancer-associated and transforming mutations within its transcriptional activation domain. Our data reveal a complex network of interactions regulating Myc destruction, and imply that enhanced protein stability contributes to oncogenic transformation by mutant Myc proteins.
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PMID:Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc. 992 31

We describe here the definition and characterization of antigen CT-8/HOM-TES-85 encoded by a previously unknown gene and identified by serological expression screening using antibodies from a seminoma patient. Intriguingly, the leucine zipper region of CT-8/HOM-TES-85 shows an atypical amphipathy with clusters of hydrophobic residues that is exclusively shared by the N-myc proto-oncogene. CT-8/HOM-TES-85 gene is tightly silenced in normal tissues except for testis. However, it is frequently activated in human neoplasms of different types including lung cancer, ovarian cancer, melanoma and glioma. Endogenous as well as heterogeneously expressed CT-8/HOM-TES-85 targets predominantly to the nucleus forming a distinctive speckled pattern of nuclear dots arranged in macromolecular structures. By co-localization studies these speckles were identified as loci of transcriptional activity and splicing, suggesting that CT-8/HOM-TES-85 may be involved in these processes. The aberrant expression of CT-8/HOM-TES-85 in human neoplasms might therefore be involved in cancer associated alterations of transcriptional or post-transcriptional processes and thus may disclose new mechanisms involved in the manifestation of the cancer phenotype.
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PMID:A novel tumour associated leucine zipper protein targeting to sites of gene transcription and splicing. 1203 26

The pKZ1 recombination mutagenesis model has provided a sensitive assay where we study somatic intrachromosomal recombination (SICR) as a mutation end-point. SICR is associated with non-homologous end-joining repair of double-strand breaks and can result in chromosomal inversions and deletions, both of which are common chromosomal aberrations identified in cancers. It has been difficult to study the effect of cancer-associated genes on chromosomal changes prior to tumour formation in vivo because of a lack of appropriate test systems. We hypothesised that cancer-associated genes play a role in formation of chromosomal aberrations and that the pKZ1 model would provide a system in which such a role could be studied in the initial steps of carcinogenesis. Transgenic tumour model mice were bred to pKZ1 mice to produce double transgenic animals. SICR inversion events were scored in mouse tissues at an early time, prior to evident tumour formation, and compared with endogenous pKZ1 SICR levels. Over-expression of the c-myc proto-oncogene resulted in a significant 2.1-fold increase in SICR in spleen. Loss of Msh2 and expression of the SV40 T antigen resulted in a significantly reduced SICR frequency (0.3 of the endogenous frequency in pKZ1 mice) in spleen and prostate respectively. Therefore SICR was affected in the case of all three cancer-associated genes studied. We hypothesise that the increase and decrease in SICR in the presence of cancer-associated genes results from incorrect repairing of double-strand breaks. The data presented here suggest that the pKZ1 model may provide a powerful tool for studying the effect of cancer-associated genes on chromosomal changes in the early stages of carcinogenesis.
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PMID:Cancer-associated genes can affect somatic intrachromosomal recombination early in carcinogenesis. 1513 36

Gallbladder carcinoma is an aggressive cancer associated with a poor prognosis. Unfortunately, the precise molecular mechanisms of development and progression of this highly malignant tumor remain unknown. It is still unclear whether loss of heterozygosity (LOH) plays a significant role in gallbladder carcinogenesis, but recent studies have found a high incidence of LOH at several chromosomes in gallbladder carcinoma. In particular, LOH on chromosomes 1p, 3p, 5p, 8p, 9p, 9q, 13q, 16q, and 17p has been highlighted and LOH on 3p, 9p, 13q, 16q, and 17p has been detected in preneoplastic lesions and in the early phase of gallbladder carcinoma during multistep carcinogenesis. The proto-oncogene, K-ras, is the best known genetic alteration in several human neoplasms, including gallbladder carcinoma. The accumulation of these genetic changes leads to a disruption in cell-cycle regulation and also continuous cell proliferation. We present an overview of K-ras alteration and LOH at several chromosome loci in gallbladder carcinoma. Further studies of the molecular mechanism in gallbladder carcinoma and the delineation of the genetic influence involved should promote our understanding of gallbladder carcinogenesis.
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PMID:Genetic alterations in gallbladder carcinoma. 1567 88

The MET proto-oncogene encodes a transmembrane tyrosine kinase receptor that mediates multiple functions such as migration, cycling and survival by binding to hepatocyte growth factor (HGF). Dysregulation of MET through inappropriate expression or mutation has been shown to play an important role in human cancers. Furthermore, inherited mutations in MET are known to contribute to the development of gastric and renal cancer in humans. Lastly, mouse models of MET mutations lead to the development of a wide variety of cancers including lymphomas, sarcomas and some forms of carcinoma. In the process of cloning canine MET, a novel germline point mutation was found in the juxtamembrane domain (G966S) in two of the templates used for cloning, both of which were derived from Rottweiler dogs, a breed believed to be at high risk for the development of several cancers. Screening of germline DNA from a variety of breeds revealed that this mutation was present in approximately 70% of Rottweiler dogs and <5% of all other breeds examined, suggesting a breed-specific heritable mutation. Stable transfection of the G966S mutant form of MET into NIH3T3 cells resulted in enhanced baseline scattering and migration of the cells, which was further increased in the presence of HGF. This study supports the notion that particular dog breeds may carry germline mutations that contribute to high rates of cancer in a manner similar to heritable, cancer-associated mutations in humans.
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PMID:Identification of a novel germline MET mutation in dogs. 1673 85

The proto-oncogene ACTR/AIB1, a coactivator for transcription factors such as the nuclear receptors and E2Fs, is frequently overexpressed in various cancers including breast cancers. However, the underlying mechanism is poorly understood. Here, we identified several functional, noncanonical E2F binding sites in the ACTR first exon and intron that are critical for ACTR gene activation. We also found that the newly identified AAA+ coregulator AAA+ nuclear coregulator cancer associated (ANCCA) is recruited to the ACTR promoter and directly controls ACTR expression in breast cancer cells. Importantly, immunohistochemistry analysis indicated that ACTR overexpression is highly correlated with the expression of E2F1 and ANCCA in a cohort of human primary and lymph node-metastasized breast cancer specimens. Along with previous findings from us and others that ACTR is involved in its own gene regulation, these results suggest that one major mechanism of ACTR overexpression in cancer is the concerted, aberrant function of the nuclear coregulators such as ANCCA and ACTR, and they point to therapeutic strategies that target the Rb-E2F axis and/or the coregulator ANCCA for ACTR-overexpressing cancers.
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PMID:Deregulated E2F and the AAA+ coregulator ANCCA drive proto-oncogene ACTR/AIB1 overexpression in breast cancer. 2012 70


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