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1.
Cancer Imaging ; 9 Spec No A: S92-7, 2009 Oct 02.
Article in English | MEDLINE | ID: mdl-19965300

ABSTRACT

OBJECTIVE: To improve patient management based on analysis of the results of a survey conducted during their visit to the imaging department of a cancer centre. MATERIALS AND METHODS: A questionnaire comprising 30 single-response questions on a dichotomous scale or a 3- or 4-modality scale was developed by three radiologists specialized in oncology, the head of our quality assurance department, a psycho-oncologist, a psycho-sociologist, a biostatistician and a member of our institute's Patient Committee. Questions concerned reception, information provided about the examinations, examination experiences, the relational qualities and availability of health care professionals, the interview with the radiologist and announcement of the examination results. RESULTS: The questionnaire was given to 190 patients in the waiting room before a standard radiography or ultrasound examination (33%), mammography and breast ultrasound (33%), computed tomography (CT) or magnetic resonance imaging (MRI) (34%). The return rate was 81%. This article analyses the responses to the various questions in terms of either percentages or detailed replies and suggestions. CONCLUSION: Analysis of the patients' experience and their suggestions provided objective elements concerning their real wishes in relation to each step of their management and identified changes and improvements to be made to the organization and daily functioning of the department.


Subject(s)
Cancer Care Facilities , Diagnostic Imaging/standards , Patient Preference , Practice Guidelines as Topic , Radiology Department, Hospital , Academies and Institutes , Adult , Aged , Aged, 80 and over , Communication , Diagnostic Imaging/psychology , Female , Humans , Magnetic Resonance Imaging/psychology , Male , Mammography/psychology , Middle Aged , Neoplasms/diagnosis , Neoplasms/psychology , Paris , Patient Satisfaction , Physician-Patient Relations , Surveys and Questionnaires , Tomography, X-Ray Computed/psychology , Truth Disclosure , Ultrasonography, Mammary/psychology , Young Adult
2.
Pathol Biol (Paris) ; 51(1): 1-4, 2003 Feb.
Article in French | MEDLINE | ID: mdl-12628285

ABSTRACT

Prostate cancer is the second cause of cancer death in men. Often, initialy hormono-independent, escape from anti-androgen therapy is a key event of tumoral progression showing an hormone-independent phenotype. To study morphological, genetic and molecular bases associated with the hormono-dependence escape, a new model of human adenocarcinoma prostate xenograft, PAC120, was established with its hormono-dependent and independent variants. Its growth was strongly inhibited by surgical castration or by administration of the new gonadotrophin-releasing hormone antagonist, FE 200486 (Ferring, San Diego, CA). Evolution to hormono-independence was frequently associated with a mucoid differentiation or a neuroendocrine-like pattern, with the apparition of new chromosomic alterations and variations of human gene expressions. PAC120 xenograft is a new model of hormone-dependent prostate cancer, opening the opportunity to study the hormone dependence escape mechanism and to evaluate the efficacity of new therapeutics.


Subject(s)
Adenocarcinoma , Paclitaxel/analogs & derivatives , Prostatic Neoplasms , Taxoids , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Animals , Docetaxel , Gonadotropin-Releasing Hormone/antagonists & inhibitors , Humans , Male , Mice , Mice, Nude , Neoplasm Transplantation , Paclitaxel/therapeutic use , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Transplantation, Heterologous
3.
Genomics ; 74(1): 79-88, 2001 May 15.
Article in English | MEDLINE | ID: mdl-11374904

ABSTRACT

We describe the isolation and characterization of NSD3, the third member of a gene family including Nsd1 and NSD2. Murine Nsd1 was isolated in a search for proteins that interact with the ligand-binding domain of retinoic acid receptor alpha. NSD2 (also known as WHSC1 and MMSET) is located in the Wolf-Hirschhorn syndrome (WHS) critical region on 4p16.3 and is involved in multiple myeloma with t(4;14) translocations. The proteins Nsd1, NSD2, and NSD3 are highly similar within a block of about 700 amino acids. This block contains several conserved domains, such as the SET domain and the PHD finger, present in proteins involved in development and/or chromatin reorganization. The NSD3 gene consists of an 8.5-kb transcript composed of 23 coding exons and spans >90 kb of genomic DNA. NSD3 maps to chromosome band 8p12 and is amplified in several tumor cell lines and primary breast carcinomas.


Subject(s)
Breast Neoplasms/genetics , Carrier Proteins/genetics , Chromosomes, Human, Pair 8/genetics , Nuclear Proteins/genetics , Alternative Splicing , Amino Acid Sequence , Binding Sites , Blotting, Northern , Breast Neoplasms/pathology , Chromosome Mapping , Cloning, Molecular , DNA, Complementary/chemistry , DNA, Complementary/genetics , Exons , Female , Gene Amplification , Gene Expression , Genes/genetics , Histone-Lysine N-Methyltransferase , Humans , In Situ Hybridization, Fluorescence , Introns , Molecular Sequence Data , Poly A/genetics , Protein Isoforms/genetics , RNA/genetics , RNA/metabolism , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Tissue Distribution , Tumor Cells, Cultured
4.
Cytogenet Cell Genet ; 88(1-2): 78-81, 2000.
Article in English | MEDLINE | ID: mdl-10773671

ABSTRACT

A family of negative regulators of JAK signaling pathway referred to as suppressor of cytokines signaling (SOCS) or cytokine-inducible SH2 protein (CIS) has been recently identified. In order to find additional members of this family, we have used a consensus amino acid sequence contained in the well-conserved central SH2 domain to search DNA databases. We isolated cDNA coding for the human homologue of SOCS-5, referred to as CIS6. Northern blot analysis revealed CIS6 mRNA expression in various tissues such as heart, muscle, spleen, and thymus and in all myeloma cell lines examined. The gene was assigned to human chromosome bands 2p21 and 3p22 by in situ hybridization. CIS6 is structurally related to other members of the CIS family and therefore could act as a negative regulator of signal transduction.


Subject(s)
Chromosomes, Human, Pair 2/genetics , Chromosomes, Human, Pair 3/genetics , Gene Expression , In Situ Hybridization, Fluorescence , Proteins/genetics , Amino Acid Sequence , Base Sequence , Cloning, Molecular , Contig Mapping , Expressed Sequence Tags , Gene Expression Profiling , Humans , Molecular Sequence Data , Proteins/chemistry , RNA, Messenger/analysis , RNA, Messenger/genetics , Sequence Alignment , Suppressor of Cytokine Signaling Proteins , Tumor Cells, Cultured , src Homology Domains/genetics
5.
Melanoma Res ; 9(4): 351-9, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10504053

ABSTRACT

Purine nucleotide metabolism was studied in two human cutaneous melanoma cell lines IPC182 and IGR221. IPC182 cells do not differentiate, while IGR221 cells differentiate spontaneously at confluency, with intense melanin production. The activities of 11 enzymes involved in the de novo or salvage synthesis or the catabolic pathway of purine nucleotides were measured at different times (from day 3 to day 18), after subculture, during exponential growth and the stationary phase, with or without differentiation. The results demonstrated remarkable differences in the enzyme activity levels and/or the evolution from exponential growth to the stationary phase for each cell line, as well as between the two cell lines. In the non-differentiating IPC182 cells, the activity of enzymes involved in purine nucleotide synthesis decreased when the growth rate slowed down and remained at a low level with a concomitant increase in catabolic activities. In the differentiating IGR221 cells, the activity of enzymes involved in purine nucleotide salvage synthesis increased during the proliferative phase and was maintained at a high level when the cells reached confluency and differentiated; catabolic activities were always lower than in the IPC182 cells. This suggests that extra purine nucleotides, synthesized preferentially by the salvage pathway, could be required for the differentiation of human melanoma cells. Since the two cell lines were cultured in the absence of any differentiation-inducing agents, these results indicate that various metabolic modifications are associated with the natural processes of cell proliferation and differentiation. This research could help to identify some of the enzymes involved in purine metabolism as the targets for the induction of differentiation.


Subject(s)
Melanoma/metabolism , Melanoma/pathology , Purines/metabolism , 5'-Nucleotidase/metabolism , Adenine Phosphoribosyltransferase/metabolism , Adenosine Deaminase/metabolism , Adenosine Kinase/metabolism , Adenylate Kinase/metabolism , Adenylosuccinate Lyase/metabolism , Aminohydrolases/metabolism , Cell Count , Cell Differentiation , Cell Division , Humans , Hypoxanthine Phosphoribosyltransferase/metabolism , IMP Dehydrogenase/metabolism , Melanins/biosynthesis , Melanins/metabolism , Melanoma/enzymology , Purine-Nucleoside Phosphorylase/metabolism , Time Factors , Tumor Cells, Cultured
6.
Diabetes ; 48(9): 1873-6, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10480622

ABSTRACT

Human alpha-endosulfine is an endogenous regulator of the beta-cell K(ATP) channels. The recombinant alpha-endosulfine inhibits sulfonylurea binding to beta-cell membranes, reduces cloned K(ATP) channel currents, and stimulates insulin secretion from beta-cells. These properties led us to study the human ENSA gene that encodes alpha-endosulfine. Here, we describe the isolation, the partial characterization, and the chromosomal localization of the ENSA gene. The ENSA gene appears to be a 1.8-kb-long sequence that contains the transcription initiation site located 528 bp upstream of the initiation codon. The ENSA gene is intronless, and a single copy gene seems to be present in the genome. Finally, the ENSA gene co-localizes on human chromosome 14 (14q24.3-q31) with a locus for susceptibility to type 1 diabetes called IDDM11; thus, the ENSA gene represents an IDDM11 candidate.


Subject(s)
Adenosine Triphosphate/pharmacology , Drosophila Proteins , Islets of Langerhans/metabolism , Peptides/genetics , Potassium Channels/drug effects , Amino Acid Sequence , Chromosome Mapping , Cloning, Molecular , Genetic Code , Humans , Intercellular Signaling Peptides and Proteins , Molecular Sequence Data , Polymerase Chain Reaction , Potassium Channels/metabolism
8.
Cytogenet Cell Genet ; 85(3-4): 297-300, 1999.
Article in English | MEDLINE | ID: mdl-10449921

ABSTRACT

The human OZF gene (ZNF146), located in chromosome band 19q13.1, is amplified and overexpressed in pancreatic carcinomas. It encodes a protein consisting solely of ten Krüppel zinc finger motifs. We report here the isolation and the characterization of the murine OZF cDNA (Zfp146). Comparison of the deduced amino acid sequences between murine, human and bovine cDNAs revealed a strong identity (95%). A closely related gene, Zfp260, was also isolated and characterized. It encodes a putative protein consisting of three vestigial zinc finger motifs followed by ten Krüppel zinc fingers sharing 79% identity and no gap insertion with the Zfp146 zinc fingers. In vitro transcription/translation of both genes led to synthesis of proteins of the predicted size. Co-expression was observed at the mRNA level in eight adult mouse tissues. Two-color FISH revealed co-localization of both genes on mouse chromosome 7 (band B1-B3). The co-expression and co-localization of Zfp146 and Zfp260 together with the close similarity of their zinc finger domains, suggests that both participate in the same regulatory pathway.


Subject(s)
DNA-Binding Proteins/genetics , Mice, Inbred BALB C/genetics , Pancreatic Neoplasms/genetics , RNA-Binding Proteins/genetics , Amino Acid Sequence , Animals , Blotting, Northern , Blotting, Southern , Blotting, Western , Chromosome Mapping , Chromosomes/genetics , Cloning, Molecular , DNA-Binding Proteins/biosynthesis , Gene Amplification , Humans , In Situ Hybridization, Fluorescence , Kruppel-Like Transcription Factors , Mice , Molecular Sequence Data , Open Reading Frames/genetics , Organ Specificity/genetics , RNA, Messenger/biosynthesis , RNA-Binding Proteins/biosynthesis , Sequence Analysis, DNA , Sequence Homology, Amino Acid
9.
Exp Cell Res ; 250(2): 499-509, 1999 Aug 01.
Article in English | MEDLINE | ID: mdl-10413603

ABSTRACT

To characterize the biological role of Kin17 protein, a mammalian nuclear protein which participates in the response to UV and ionizing radiation and binds to curved DNA, EBV-derived vectors carrying (Mm)Kin17 cDNA were constructed and transfected in tumorigenic cells harboring different p53 profiles (HeLa, H1299, and HCT116) and in immortalized HEK 293 cells. (Mm)Kin17 protein expression induced a tremendous decrease in cell proliferation of the three tumorigenic cell lines 2 weeks after transfection. Transfection of HEK 293 cells with an pEBVCMV(Mm)Kin17 plasmid gave rise to numerous (Mm)Kin17-expressing cells which constantly disappeared with time, preventing the establishment of (Mm)Kin17-expressing cells. Several independent clones were isolated from HEK 293 cells carrying a pEBVMT(Mm)Kin17 vector. The two clones described here (B223.1 and B223.2) exhibited different (Mm)Kin17 protein levels and displayed a gradual decrease in their proliferative capacities. In B223.1 cells, the basal expression of (Mm)Kin17 greatly reduced plating efficiency and cell growth. B223.1 cell morphology was altered, with numerous round-shaped cells whose spreading on the culture support was hampered. We observed giant multinucleated cells or cells containing micronuclei-like structures and/or multilobed nuclei. To conclude, (Mm)Kin17 overexpression reduced the proliferation of tumorigenic cells independently of their p53 status and modified cell growth and cell morphology of established HEK 293 cells producing (Mm)Kin17 protein. It is likely that (Mm)Kin17 may interfere with DNA replication.


Subject(s)
Cell Division , DNA-Binding Proteins/physiology , Nuclear Proteins , Animals , Blotting, Western , Cadmium/pharmacology , Cell Count , Cell Line, Transformed , Cell Size , Clone Cells/cytology , Clone Cells/drug effects , Clone Cells/metabolism , Cyclin B/metabolism , DNA-Binding Proteins/genetics , Fluorescent Antibody Technique, Indirect , Gene Expression/drug effects , Giant Cells/metabolism , Humans , In Situ Hybridization, Fluorescence , Mice , Proliferating Cell Nuclear Antigen/metabolism , RNA-Binding Proteins , Transfection , Tumor Cells, Cultured , Tumor Suppressor Protein p53/metabolism , Zinc/pharmacology
10.
J Biol Chem ; 274(25): 17860-8, 1999 Jun 18.
Article in English | MEDLINE | ID: mdl-10364231

ABSTRACT

Poly(ADP-ribosylation) is a post-translational modification of nuclear proteins in response to DNA damage that activates the base excision repair machinery. Poly(ADP-ribose) polymerase which we will now call PARP-1, has been the only known enzyme of this type for over 30 years. Here, we describe a cDNA encoding a 62-kDa protein that shares considerable homology with the catalytic domain of PARP-1 and also contains a basic DNA-binding domain. We propose to call this enzyme poly(ADP-ribose) polymerase 2 (PARP-2). The PARP-2 gene maps to chromosome 14C1 and 14q11.2 in mouse and human, respectively. Purified recombinant mouse PARP-2 is a damaged DNA-binding protein in vitro and catalyzes the formation of poly(ADP-ribose) polymers in a DNA-dependent manner. PARP-2 displays automodification properties similar to PARP-1. The protein is localized in the nucleus in vivo and may account for the residual poly(ADP-ribose) synthesis observed in PARP-1-deficient cells, treated with alkylating agents or hydrogen peroxide.


Subject(s)
DNA Damage/genetics , Poly(ADP-ribose) Polymerases/genetics , 3T3 Cells , Amino Acid Sequence , Animals , Chromosome Mapping , Chromosomes, Human, Pair 14/genetics , Cloning, Molecular , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , Enzyme Activation/genetics , Humans , In Situ Hybridization, Fluorescence , Lymphocytes/enzymology , Mice , Molecular Sequence Data , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Poly(ADP-ribose) Polymerases/chemistry , RNA, Messenger/metabolism , Recombinant Proteins/genetics , Sequence Alignment
13.
Genes Chromosomes Cancer ; 23(2): 100-8, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9739012

ABSTRACT

Cytogenetic analyses were performed on 223 breast carcinomas, of which 60% contained homogeneously staining regions (hsr), an intrachromosomal cytogenetic feature of gene amplification. The precise hsr localization could be determined for 123 hsr from 72 cases. The juxtacentromeric region of chromosome 8, band 11q13, and the whole of chromosome 17 were frequently involved. For 28 cases, the origin of the DNA sequences forming HSR could be investigated by chromosome painting, comparative genomic hybridization, and/or Southern blotting. Sequences from chromosomes 11 and 17 were mostly found within hsr located on chromosomes 11 and 17, respectively. In contrast, sequences from chromosome 8 were rarely found within hsr localized on chromosome 8. These observations suggest that different mechanisms lead to hsr formation in breast cancer. Band 11 q13 and the 17p chromosome arm may correspond to sites of in situ amplification driven by deletions distal to the amplification target genes. hsr in the region 17q2, which is also a frequent site of in situ amplification, takes place without the occurrence of a distal deletion. The short arm of chromosome 8 is often deleted, but frequently becomes the site of hsr formed elsewhere in the genome.


Subject(s)
Breast Neoplasms/genetics , Carcinoma/genetics , Neoplasm Recurrence, Local/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Breast Neoplasms/chemistry , Carcinoma/chemistry , Chromosome Breakage , Chromosomes, Human, Pair 11/chemistry , Chromosomes, Human, Pair 17/chemistry , Chromosomes, Human, Pair 8/chemistry , Female , Genome, Human , Humans , Karyotyping , Middle Aged , Neoplasm Recurrence, Local/chemistry , Staining and Labeling
14.
Genomics ; 52(1): 62-71, 1998 Aug 15.
Article in English | MEDLINE | ID: mdl-9740672

ABSTRACT

We have developed approaches for the cloning of minisatellites from total genomic libraries and applied these approaches to the human, rat, and pig genomes. The chromosomal distribution of minisatellites in the three genomes is strikingly different, with clustering at chromosome ends in human, a seemingly almost even distribution in rat, and an intermediate situation in pig. A closer analysis, however, reveals that interstitial sites in pig and rat often correspond to terminal cytogenetic bands in human. This observation suggests that minisatellites are created toward chromosome ends and their internalization represents secondary events resulting from rearrangements involving chromosome ends.


Subject(s)
Evolution, Molecular , Genome , Minisatellite Repeats/genetics , Sequence Analysis, DNA , Telomere/genetics , Animals , Base Sequence , Chromosome Mapping , Cloning, Molecular/methods , Gene Frequency , Humans , In Situ Hybridization, Fluorescence , Molecular Sequence Data , Rats , Swine
15.
Mol Cell Biol ; 18(8): 4924-34, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9671500

ABSTRACT

The highly conserved SR family contains a growing number of phosphoproteins acting as both essential and alternative splicing factors. In this study, we have cloned human genomic and cDNA sequences encoding a novel SR protein designated SRp46. Nucleotide sequence analyses have revealed that the SRp46 gene corresponds to an expressed PR264/SC35 retropseudogene. As a result of mutations and amplifications, the SRp46 protein significantly differs from the PR264/SC35 factor, mainly at the level of its RS domain. Northern and Western blot analyses have established that SRp46 sequences are expressed at different levels in several human cell lines and normal tissues, as well as in simian cells. In contrast, sequences homologous to SRp46 are not present in mice. In vitro splicing studies indicate that the human SRp46 recombinant protein functions as an essential splicing factor in complementing a HeLa cell S100 extract deficient in SR proteins. In addition, complementation analyses performed with beta-globin or adenovirus E1A transcripts and different splicing-deficient extracts have revealed that SRp46 does not display the same activity as PR264/SC35. These results demonstrate, for the first time, that an SR splicing factor, which represents a novel member of the SR family, is encoded by a functional retropseudogene.


Subject(s)
Alternative Splicing , Phosphoproteins/genetics , Pseudogenes , 3T3 Cells , Amino Acid Sequence , Animals , Base Sequence , COS Cells , Cell Line , Chlorocebus aethiops , DNA, Complementary , Gene Expression , HL-60 Cells , HeLa Cells , Humans , Mice , Molecular Sequence Data , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , Serine-Arginine Splicing Factors
16.
Proc Natl Acad Sci U S A ; 95(15): 8835-40, 1998 Jul 21.
Article in English | MEDLINE | ID: mdl-9671765

ABSTRACT

We previously reported the identification of mZac, a novel mouse zinc finger protein that shared with p53 the ability to regulate concomitantly apoptosis and cell cycle progression. We describe here the isolation, chromosomal localization, and functional in vitro characterization of its human homolog. hZAC is a widely expressed zinc finger protein that reveals transactivation and DNA-binding activity. hZAC inhibits tumor cell growth through induction of apoptotic cell death and G1 arrest. Thus hZAC, like its mouse counterpart, displays antiproliferative properties through pathways known to be central to the activity of p53. We mapped hZAC on chromosome 6q24-q25, a region frequently deleted in many solid tumors. Indeed, allelic loss at 6q24-q25 has been shown in breast and ovary cancers, melanomas, astrocytomas, and renal cell carcinomas. Furthermore, Abdollahi et al. [Abdollahi, A., Godwin, A. K., Miller, P. D., Getts, L. A., Schultz, D. C., Tagushi, T., Testa, J. R. & Hamilton, T. C. (1997) Cancer Res. 57, 2029-2034] recently isolated ZAC through its loss of expression in a surface epithelial ovary tumor model and accordingly named it Lot for "lost on transformation." In view of these observations, the functional properties we report here provide further arguments to consider hZAC as a tumor suppressor gene candidate.


Subject(s)
Cell Cycle Proteins/genetics , Chromosomes, Human, Pair 6 , Genes, Tumor Suppressor , Neoplasms/genetics , Trans-Activators/genetics , Transcription Factors , Zinc Fingers/genetics , Amino Acid Sequence , Animals , Apoptosis/genetics , Blotting, Southern , Cell Cycle Proteins/chemistry , Cell Cycle Proteins/metabolism , Chromosome Mapping , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Humans , Mice , Molecular Sequence Data , Neoplasms/pathology , Sequence Homology, Amino Acid , Trans-Activators/chemistry , Trans-Activators/metabolism , Transcriptional Activation , Tumor Cells, Cultured , Tumor Suppressor Proteins
17.
Free Radic Res ; 29(6): 487-97, 1998 Dec.
Article in English | MEDLINE | ID: mdl-10098454

ABSTRACT

8-Hydroxyguanine (8-OH-Gua) is a major mutagenic lesion produced on DNA by the oxidative stress induced by either the endogen metabolism or the exposure to external agents. In bacteria and yeast this modified base can be removed by specific DNA glycosylases. Recently a human gene coding for an 8-OH-Gua DNA glycosylase/AP lyase has been identified by its homology to the yeast OGG1. This gene is located in human chromosome 3p25, a region commonly rearranged in various cancers, specially in lung tumor cells. We report here the cloning, by sequence homology to the yeast OGG1, of a mouse cDNA coding for a 8-OH-Gua DNA glycosylase with 84% and 38% identity to the human and yeast relevant proteins, respectively. The Ogg1 gene is localized to the mouse chromosome 6E. The mouse Qgg1 cDNA, when expressed in Eschierichia coli, is capable of suppressing the spontaneous mutator phenotype of a DNA repair deficient fpg mutgamma strain. The mouse Ogg1 protein acts efficiently on duplexes in which the 8-OH-Gua is paired with a cytosine but is inactive on 8-OH-Gua: Ade pair, consistently with its proposed biological role in the avoidance of mutations. A comparison of the mouse enzyme with other eukaryotic Ogg1 enzymes is also presented. The isolation of this gene will allow the development of an animal model to study the effects of oxidative stress on carcinogenesis and degenerative diseases.


Subject(s)
DNA Repair , Escherichia coli Proteins , Guanine/analogs & derivatives , N-Glycosyl Hydrolases/genetics , N-Glycosyl Hydrolases/metabolism , Amino Acid Sequence , Animals , Chromosome Mapping , Cloning, Molecular , DNA-Formamidopyrimidine Glycosylase , Escherichia coli/genetics , Fungal Proteins/genetics , Genetic Complementation Test , Guanine/metabolism , Humans , Mice , Molecular Sequence Data , Sequence Homology, Amino Acid , Yeasts/genetics
18.
Genomics ; 42(1): 141-5, 1997 May 15.
Article in English | MEDLINE | ID: mdl-9177784

ABSTRACT

Interleukin-13 (IL-13) is a cytokine secreted by activated T cells and shares most but not all biological activities with interleukin-4 (IL-4). Both cytokines play an important role as a switch factor directing synthesis of IgE; they act on monocytes and endothelial cells, but unlike IL-4, IL-13 does not act on T cells. These cytokines have both common and distinct components in their respective receptors. Based on sequence similarity shared by cytokine receptor family members, we have identified a cDNA encoding the human IL-13 receptor (IL-13R). This cDNA was used to examine the pattern of IL-13R mRNA expression by Northern blot analyses of poly(A)+ RNA purified from different human tissues and cell lines. Among several myeloma cell lines analyzed, the U266 cell line was the only one found to express IL-13R transcripts. This cell line is also the only one described as producing IgE. The IL-13R gene was mapped to chromosome Xq24 by in situ hybridization. Interestingly, this locus is near that of the CD40 ligand gene, the product of which is also involved, like IL-13, in proliferation and IgE isotype switching of human B cells. The human IL-13R gene maps between two cytokine receptor genes located on the chromosome arm Xq region: the interleukin-2 receptor gamma chain gene (Xq13.1) and the interleukin-9 receptor gene (Xq28). The lack of nucleotide sequence similarity suggests unrelated evolutionary pathways between these receptor genes.


Subject(s)
Receptors, Interleukin/genetics , Amino Acid Sequence , Base Sequence , Cell Line , Chromosome Mapping , DNA, Complementary/genetics , Evolution, Molecular , Gene Expression , Humans , In Situ Hybridization, Fluorescence , Interleukin-13/metabolism , Interleukin-13 Receptor alpha1 Subunit , Interleukin-9/metabolism , Molecular Sequence Data , Multiple Myeloma/genetics , Multiple Myeloma/immunology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Interleukin-13 , Receptors, Interleukin-2/genetics , Receptors, Interleukin-9 , Tissue Distribution , Tumor Cells, Cultured , X Chromosome/genetics
20.
Br J Cancer ; 74(6): 839-45, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8826847

ABSTRACT

Loss of chromosome 10 was observed in 10 out of 12 xenografted glioblastomas studied. Chromosome 10 carries the gene coding the hexokinase type 1 isoenzyme (HK-I), which catalyses the first step of glycolysis, which is essential in brain tissue and glioblastomas. We investigated the relationships between the relative chromosome 10 number, the amount of HK-I mRNA, HK-I activity and its intracellular distribution, and glycolysis-related parameters such as the lactate-pyruvate ratio, lactate dehydrogenase (LDH) and ATP contents. Individual tumour HK-I mRNA amounts were 23-65% lower than that of normal human brain and reflected the relative decrease of chromosome 10 number (alpha < 0.01). Total HK activities of individual glioblastomas varied considerably but were constantly (a mean of seven times) lower than that of normal brain tissue. The mitochondria-bound HK-I fraction of individual tumours was generally over 50%, compared with that of normal brain tissue. As shown by lactate - pyruvate ratios, in all the gliomas, glycolysis was elevated to an average of 3-fold that measured in normal brain. An elevated ATP content was also constantly noted. Adaptation of glioblastoma metabolism to the chromosome 10 loss and to the HK-I transcription unit emphasises the critical role of glycolysis in their survival. We hypothesise that HK-I, the enzyme responsible for initiating glycolysis necessary for brain function, may approach its lowest limit in gliomas, thereby opening therapeutic access to pharmacological anti-metabolites affecting energy metabolism and tumour growth.


Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 10 , Glioma/genetics , Glycolysis , Hexokinase/genetics , Adenosine Triphosphate/metabolism , Glioma/metabolism , Hexokinase/metabolism , Humans , L-Lactate Dehydrogenase/metabolism , Lactic Acid/metabolism , Pyruvic Acid/metabolism , RNA, Messenger/analysis
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