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

Cancer chemotherapeutic agents primarily act by damaging cellular DNA directly or indirectly. Tumor cells, in contrast to normal cells, respond to cisplatin with transient gene expression to protect and/or repair their chromosomes. Repeated cisplatin treatments results in a stable resistant cell line with enhanced gene expression but lacking gene amplification for the proteins that will limit cisplatin cytotoxicity. Recently, several new human cell lines have been characterized for cisplatin resistance. These cell lines have led to a better understanding of the molecular and biochemical basis of cisplatin resistance. The c-fos proto-oncogene, a master switch for turning on other genes in response to a wide range of stimuli, has been shown to play an important role in cisplatin resistance both in vitro and in patients. Based on these studies, new strategies have been developed to circumvent and/or exploit clinical cisplatin resistance.
 ...
PMID:Cisplatin resistance in human cancers. 182 May 82

The glutathione S-transferase gene (GST pi) is located on the same chromosome band (11q13) as proto-oncogenes INT2 and HSTF1 which are frequently amplified in breast cancer. Using the Southern blot technique, we looked for the amplification of the GST pi gene in 17 fresh tumors from human mammary carcinoma. The tumors were preselected because either they had an amplification of the INT2 proto-oncogene detected by dot blot, or their karyotypes exhibited or did not exhibit homogeneously staining regions, a cytogenetic character indicating amplification. Coamplification of GST pi, HSTF1 and INT2 was observed in five tumors, and coamplification of GST pi and HSTF1 without amplification of INT2 in another tumor. We also observed coamplification of GST pi, INT2, HSTF1 in the mammary carcinoma cell line MDA/MB134, whereas GST pi alone was amplified in the mammary epithelial cell line HBL100. These results indicate that INT2, HSTF1 and GST pi belong to the same large amplicon. Since GST pi is involved in intracellular detoxication and since chemotherapeutic drugs are among its substrates, it will be of interest to study GST pi gene expression as well as the response to chemotherapy in patients presenting this amplicon.
 ...
PMID:GST pi gene is frequently coamplified with INT2 and HSTF1 proto-oncogenes in human breast cancers. 182 46

We have detected transforming activity by a tumorigenicity assay using NIH3T3 cells transfected with DNA from a chronic myeloproliferative disorder patient. Here, we report the cDNA cloning of the corresponding oncogene, designated UFO, in allusion to the as yet unidentified function of its protein. Nucleotide sequence analysis of a 3116bp cDNA clone revealed a 2682-bp-long open reading frame capable of directing the synthesis of a 894 amino acid polypeptide. The predicted UFO protein exhibits characteristic features of a transmembrane receptor with associated tyrosine kinase activity. The UFO proto-oncogene maps to human chromosome 19q13.1 and is transcribed into two 5.0 kb and 3.2 kb mRNAs in human bone marrow and human tumor cell lines. The UFO locus is evolutionarily conserved between vertebrate species. A 4.0 kb mRNA of the murine UFO homolog is expressed in a variety of different mouse tissues. We thus have identified a novel element of the complex signaling network involved in the control of cell proliferation and differentiation.
 ...
PMID:A novel putative tyrosine kinase receptor with oncogenic potential. 183 74

The melanoma inducing locus of Xiphophorus encodes a tumorigenic version of a novel putative receptor tyrosine kinase (Xmrk). To elucidate the mechanism of oncogenic activation of Xmrk, we compared the structure and expression of two oncogenic loci with the corresponding proto-oncogene. Only minor structural alterations were found to be specific for the oncogenic Xmrk genes. Marked overexpression of the oncogene transcripts in melanoma, which are approximately 1 kb shorter than the proto-oncogene transcript, correlates with the malignancy of the tumors. The tumor transcripts are derived from an alternative transcription start site that is used only in the oncogenic loci. Thus, oncogenic activation of the melanoma inducing Xmrk gene appears primarily to be due to novel transcriptional control and overexpression.
 ...
PMID:Transcriptional activation of the melanoma inducing Xmrk oncogene in Xiphophorus. 184 57

The t(14;18) chromosomal translocation that results in the juxtaposition of the bcl-2 proto-oncogene with the heavy chain JH locus is a common cytogenetic abnormality in human lymphoma. In particular, it is seen in about 85% of follicular lymphoma (FL) and up to one-third of diffuse lymphomas (DL). The chromosome 18 breakpoints have been shown to cluster into two regions. The major breakpoint region (mbr) within the 3' untranslated region of the bcl-2 proto-oncogene accounts for approximately 60% of the cases and the minor cluster region (mcr) 30 kb 3' of bcl-2 accounts for approximately 25% of the breakpoints. Because of variability in the position of the breakpoint, detection of the t(14;18) by Southern blot analysis provides an important clonal marker for the tumor. However, conventional electrophoresis (CE) fails to detect the translocation in 15% to 25% of cases. We have applied pulsed-field gel electrophoresis (PFGE) to the detection of the t(14;18) in a series of lymphoma prospectively analyzed by CE, polymerase chain reaction (PCR), and cytogenetic analysis. PFGE readily detected t(14;18) rearrangements as indicated by comigration of bands detected with probes for the mbr region (chromosome 18) and the JH locus (chromosome 14). In a series of 40 patients with FL, this method proved to be the most comprehensive for detection of the translocation compared with standard methods; in fact, in one case only PFGE was able to detect the chromosomal rearrangement. Ten percent of the FL cases were negative by all methods tested. In a separate analysis of matched tissue specimens from cases of tumor progression of FL to diffuse lymphoma, PFGE detected a common t(14;18) rearrangement confirming a clonal origin in seven of seven cases, whereas CE detected a rearrangement in only three of seven cases. Overall, PFGE was able to detect a translocation in 8 of 12 cases that were negative by CE and four of eight negative by cytogenetic analysis. In conclusion, PFGE analysis is more comprehensive than CE, PCR, and cytogenetic analysis for the detection of the t(14;18) breakpoint in tissue biopsies of malignant lymphoma.
 ...
PMID:Enhanced detection of the t(14;18) translocation in malignant lymphoma using pulsed-field gel electrophoresis. 188 22

The t(9;22) Philadelphia chromosome translocation fuses 5' regulatory and coding sequences of the BCR gene to the c-ABL proto-oncogene. This results in the formation of hybrid BCR-ABL mRNAs and proteins. The shift in ABL transcriptional control to the BCR promoter may play a role in cellular transformation mediated by this rearrangement. We have functionally localized the BCR promoter to a region 1 kb 5' of BCR exon 1 coding sequences by using a chloramphenicol acetyltransferase reporter gene assay. Nucleotide sequence analysis of this region revealed many consensus binding sequences for transcription factor SP1 as well as two potential CCAAT box binding factor sites and one putative helix-loop-helix transcription factor binding site. No TATA-like or "initiator" element sequences were found. Because of low steady-state levels of BCR mRNA and the high GC content (78%) of the promoter region, definitive mapping of transcription start sites required artificial amplification of BCR promoter-directed transcripts. Overexpression from the BCR promoter in a COS cell system was effective in demonstrating multiple transcription initiation sites. In order to assess the effects of chromosomal translocation on the transcriptional control of the BCR gene, we determined S1 nuclease protection patterns of poly(A)+ RNA from tumor cell lines. No differences were observed in the locations and levels of BCR transcription initiation sites between those lines that harbored the t(9;22) translocation and those that did not. This demonstrates that BCR promoter function remains intact in spite of genomic rearrangement. The BCR promoter is structurally similar to the ABL promoters. Together, this suggests that the structural fusion of BCR-ABL and not its transcriptional deregulation is primarily responsible for the transforming effect of the t(9;22) translocation.
 ...
PMID:Characterization of the BCR promoter in Philadelphia chromosome-positive and -negative cell lines. 190 Sep 18

The central neurocytoma, a recently identified rare supratentorial brain tumor in young adults, is characterized by intraventricular location and a usually benign clinical course. In order to elucidate the histogenesis and differentiation potential of this neoplasm, we have undertaken an immunocytochemical and molecular biological study of four central neurocytomas. It was found by immunocytochemistry and immunoblotting that all tumors express neuron-specific enolase and synaptophysin. Western blots also revealed expression of the synaptic vesicle protein, synapsin I, neurofilament protein and glial fibrillary acidic protein in several neurocytomas which failed to exhibit immunoreactivity to these marker antigens on paraffin sections. Immunocytochemical reactions with antibodies to synaptophysin and glial fibrillary acidic protein on adjacent sections demonstrated coexpression in individual tumor cells. The neuronal form of the pp60src protein-tyrosine kinase, an oncogene-product specifically expressed in central nervous system neurons, was not detectable in two central neurocytomas investigated. N-myc, a proto-oncogene frequently amplified in childhood neuroblastomas, was present as a single copy gene in all central neurocytomas, indicating that amplification of this gene is not involved in the pathogenesis of the central neurocytoma. In accordance with ultrastructural evidence of synaptogenesis, we conclude that the central neurocytoma is a neuroectodermal tumor with consistent commitment for neuronal differentiation. Since these tumors retain a potential for additional glial differentiation, we propose an origin from bipotential progenitor cells in the periventricular matrix, which in the mammalian brain persists throughout adult life.
 ...
PMID:Histogenesis and differentiation potential of central neurocytomas. 190 27

The transforming potential of acrylonitrile epoxide (ANO) was tested in a modified NIH3T3 transfection-transformation assay. This involves a new ras construct obtained by ligating a human c-Ha-ras-1 proto-oncogene to the pSV2neo mammalian vector. The new plasmid was allowed to react with ANO or an established carcinogen in vitro, and the modified ras DNA transfected into NIH 3T3 cells. The transfectants are subjected to triple selections: G418 (neomycin) resistance, low serum growth, and limit dilutions. The end points are scored by cell growth kinetics and monolayer saturation density. In using this protocol, the EJ tumor ras plasmid was the positive control, and anti-benzo[a]pyrene-7,8- dihydrodiol-9,10-epoxide (anti-BPDE) and N-methyl-N-nitrosourea were found to be positive in yielding transformants. Although ANO-modified ras gave rise to two G418R clones, both were scored negative due to their normal growth rate and monolayer density similar to the negative controls. Southern blot analysis of anti-BPDE transformant DNA revealed a fragment of 411 bp, indicating a ras mutation at codon 11 or 12. However, both the ANO clones showed the wild-type band of 355 bp by the same method.
 ...
PMID:Inactivity of acrylonitrile epoxide to modify a Ha-ras DNA in a non-focus transfection-transformation assay. 190 90

Experiments were performed to determine the effect of neonatal estrogen treatment on the expression of the proto-oncogene c-fos in the BALB/c mouse cervicovaginal tract. Estradiol induces the expression of c-fos in the normal mouse cervicovaginal tract. However, c-fos expression was not stimulated by estradiol in the cervicovaginal tracts of mice that received neonatal estrogen treatment. In addition, the level of expression of c-fos by the estrogen- and progesterone-induced murine cervicovaginal LJ6195 tumor was similar to that in the normal vaginal tract following estradiol stimulation and was not regulated by estradiol.
 ...
PMID:Alteration of proto-oncogene c-fos expression in neonatal estrogenized BALB/c female mice & murine cervicovaginal tumor LJ6195. 191 5

Although analogies are often made comparing development to cancer, there is of course a major difference. Normal development requires complex patterns of rigidly controlled cell proliferation and differentiation. In contrast, cancer represents the pathological condition that results when normal cell growth patterns are uncoupled from their regulatory influences. Genetic studies of RNA tumor viruses have provided insights into the relationships and differences of the genes responsible for normal development and cancer. The presence of discrete genes (oncogenes) within the genome of oncogenic retroviruses is responsible for their tumorigenic potential. Molecular genetic studies have found that normal eukaryotic cells possess genes that are quite homologous to the retroviral oncogenes. These normal cellular genes (proto-oncogenes) are involved in the regulation of proliferation and differentiation. However, if mutated, proto-oncogenes have the potential for inducing neoplastic transformation. The conversion of a proto-oncogene to an oncogene is called activation. Proto-oncogenes can become activated by a variety of genetic mechanisms including transduction, insertional mutagenesis, amplification, point mutations, and chromosomal translocations. In each instance the genetic aberration results in a proto-oncogene that is now free of its normal regulatory constraints. Such deregulation of function imparts a distinct growth advantage to the cell.
 ...
PMID:Proto-oncogenes in development and cancer. 193 Jun 40


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>