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Biomedical subjects

S Ingvarsson

Publications and source records attributed to S Ingvarsson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Identification of a breast tumor with microsatellite instability in a potential carrier of the hereditary non-polyposis colon cancer trait.

Allelic expansion at microsatellite loci in colorectal tumor DNA indicates a genomic instability caused by defects in DNA mismatch repair. This is observed in a high proportion of tumors from individuals affected by hereditary non-polyposis colorectal carcinoma, but to a lesser extent in sporadic colorectal tumors. In this study we screened 46 colorectal tumors for replication errors (RER). Tumors from six patients were found to be RER positive, two of which had a marked family history of colon cancer. In both cases the RER + phenotype was detected in colon tumors from other family members, suggesting a germline mutation in mismatch repair genes. Additionally, RER + phenotype, distinct from that of the colon and sporadic breast tumors, was found in malignant breast tissue from the mother of one proband.

Adult↗
PubMed1991

Chromosomal assignment of retinoic acid receptor (RAR) genes in the human, mouse, and rat genomes.

The human genes encoding the alpha and beta forms of the retinoic acid receptor are known to be located on chromosomes 17 (band q21.1:RARA) and 3 (band p24:RARB). By in situ hybridization, we have now localized the gene for retinoic acid receptor gamma, RARG, on chromosome 12, band q13. We also mapped the three retinoic acid receptor genes in the mouse, by in situ hybridization, on chromosomes 11, band D (Rar-a); 14, band A (Rar-b); and 15, band F (Rar-g), respectively, and in the rat, using a panel of somatic cell hybrids that segregate rat chromosomes, on chromosomes 10 (RARA), 15 (RARB), and 7 (RARG), respectively. These assignments reveal a retention of tight linkage between RAR and HOX gene clusters. They also establish or confirm and extend the following homologies: (i) between human chromosome 17, mouse chromosome 11, and rat chromosome 10 (RARA); (ii) between human chromosome 3, mouse chromosome 14, and rat chromosome 15 (RARB); and (iii) between human chromosome 12, mouse chromosome 15, and rat chromosome 7 (RARG).

Animals↗
PubMed1991

Chromosomal assignment of five cancer-associated rat genes: two thyroid hormone receptor (ERBA) genes, two ERBB genes and the retinoblastoma gene.

Using a panel of somatic cell hybrids that segregate rat chromosomes, the localization of five cancer-related rat genes was determined: (i) two thyroid receptor genes, THRA1/ERBA1 and THRB/ERBA2 on chromosomes 10 and 15 respectively, (ii) two ERBB genes, namely the epidermal growth factor gene (EGFR, also called ERBB1) and the ERBB2 gene (also designated neu) on chromosomes 14 and 10 respectively, and (iii) the retinoblastoma gene, RB1, on chromosome 15. The THRA1/ERBA1 and ERBB2/neu genes are thus included in a synteny group, conserved on rat chromosomes 10 and human chromosome arm 17q.

Alleles↗
PubMed1990

Differences in c-myc and pvt-1 amplification in SEWA sarcoma sublines selected for adherent or non-adherent growth.

Conversion of solid sarcomas and carcinomas into ascites tumors depends on the in vivo selection of phenotypically altered tumor cell variants that can grow in the dissociated form. Once selected, they retain this property even after prolonged s.c. growth as solid tumors. From an s.c.-passaged subline of an ascites-converted murine sarcoma (SEWA-AS12), we were able to separate cells adapted to the ascites form of growth from cells that can only grow in the solid form on the basis of their differential adherence to plastic. Both c-myc and pvt-1 were amplified approximately 63- to 77-fold in the nonadherent subline (SEWA-AS12-NA), but only 5- to 8-fold in the adherent subline (SEWA-AS12-ADH). This suggests that c-myc and/or pvt-1 amplification may provide a selective advantage to cells that can grow in the dissociated form.

Animals↗
PubMed1990

Recombinant plasmid expressing the entire coding region of the Bmyc putative protein.

An expression vector with the entire coding region of Bmyc oncogene was constructed. The longest predicted open reading frame of Bmyc (178 amino acid residues) was expressed as a fusion protein with the trpE protein (308 amino acid residues) in transformed bacteria. The newly synthesized 58 Kd protein reacted with an anti pan-myc serum. The fusion protein isolated from a preparative Western blot was used as immunogen to generate rabbit anti myc specific immune sera.

Animals↗
PubMed1990

The myc gene family proteins and their role in transformation and differentiation.

Several genes within the mammalian genome share homology with the transforming gene, v-myc, of the avian myelocytic leukemia viruses. Of these, c-myc, Nmyc and Lmyc have been shown to possess transforming activity in vitro and each is found to be aberrantly expressed in a variety of tumours. In normal tissues, expression of Nmyc and Lmyc is restricted to embryonic development and a few adult tissues whereas c-myc and Bmyc are very widely expressed. The proteins encoded by the various myc genes share substantial sequence homology. c-, N and Lmyc proteins are all nuclear phosphoproteins that possess very short biological half lives and bind DNA. All three possess identifiable motifs present in a number of other nuclear proteins involved in transcriptional regulation, and the possible role of myc proteins in gene regulation is discussed. Some experiments, however, favour a different role for c-myc, in DNA replication. Whatever their precise molecular functions may be, it is clear that myc genes play an essential role in the regulation of cellular proliferation.

Animals↗
PubMed1990

A gene near the D3F15S2 site on 3p is expressed in normal human kidney but not or only at a severely reduced level in 11 of 15 primary renal cell carcinomas (RCC).

Renal Cell Carcinoma (RCC) has been associated with the loss of heterozygosity at several loci on the short arm of chromosome 3 (3p). We have previously found that one of these loci, D3F15S2 (pH3H2) was lost in 76% of the tumor cells derived from heterozygous donors (Kovacs, G., Erlandsson, R., Boldog, F., Ingvarrsson, S., Müller-Brechlin, R., Klein, G. & Sümegi, J. (1988), Proc. Natl. Acad. Sci., 85, 1571-5). More recently we have identified a putative CpG island in the vicinity of D3F15S2, suggesting that DNA sequences in or around this site may have coding potential (Boldog, F., Erlandsson, R., Klein, G. & Sümegi, J. (1989). Cancer Genet. Cytogenet., 42, 295-306). The screening of a human placenta cDNA library with DNA probes derived from D3F15S2 has led to the isolation of several cDNA clones. They identified a 2.9 Kb long message in human placenta and kidney. In total RNA from 11 of 15 primary RCCs the gene expression was reduced to less than 20% compared to eight normal kidneys. This low level of expression may be due to contaminating normal tissue. In the remaining 4 tumors the expression varied from 24-51% compared to normal kidney. To facilitate reference, the gene was provisionally designated as 'RIK'. It was expressed in the HEK 293, one osteosarcoma (HOS), two carcinoma (COLO320 and QDMT), and three Burkitt lymphoma lines (BL2, BL29 and BL31). It was not expressed in one Burkitt lymphoma (DG75) and two EBV transformed lymphoblastoid cell lines (LCL) (NAD-20 and Cherry).

Carcinoma, Renal Cell↗
PubMed1989

Nucleotide sequence of the rat Bmyc gene.

We have cloned and sequenced the rat Bmyc gene. The rat Bmyc gene contains sequences related to the central part of c-myc, namely the first intron, the second exon, and the noncoding part of the third exon. The homology drops in the 3' part of the c-myc second exon, but continues in the noncoding part of the third exon. We have sequenced the total predicted coding region of the Bmyc. The longest open reading frame in Bmyc suggests a protein of 178 amino acids, which is only 41% of the c-myc protein size. To confirm the putative open reading frame, we have produced a trpE-Bmyc protein that is detected with a pan-myc antibody. We discuss these findings in the context of potential functional domains and the possibility of overlapping and distinct activities of myc-family proteins.

Amino Acid Sequence↗
PubMed1988

Rat c-raf oncogene is located on chromosome 4 and may be activated by sequences from chromosome 13.

Activated forms of the protooncogene c-raf have been found to transform established lines of rodent fibroblasts after transfection with DNA from several human and rat tumors. Using Southern blot analysis of DNAs from rat x mouse somatic cell hybrids, we have mapped c-raf to rat chromosome 4. An exogenous sequence that was found juxtaposed to c-raf within transforming DNA originally derived from a rat hepatocellular carcinoma was localized to chromosome 13.

Animals↗
PubMed1988

Consistent chromosome 3p deletion and loss of heterozygosity in renal cell carcinoma.

Renal cell carcinoma (RCC) and normal kidney tissues have been examined from 34 patients with sporadic, nonhereditary RCC. Eighteen of the 21 cytogenetically examined tumors (86%) had a detectable anomaly of chromosome arm 3p distal to band 3p11.2-p13, manifested as a deletion, combined with the nonreciprocal translocation of a segment from another chromosome or monosomy 3. Restriction-fragment-length polymorphism analysis showed loss of D1S1 heterozygosity in 16 of the 21 cases (76%). D3S2 heterozygosity was lost in 2 of 11 cases (18%). The variability of the breakpoint between 3p11.2 and 3p13 and the absence of a consistently translocated segment from another chromosome suggests a genetic-loss mechanism, while the activation of a dominant oncogene appears less likely. Together with the previously demonstrated involvement of the 3p14.2 region in a familial case, these findings suggest that RCCs may arise by the deletion of a "recessive cancer gene," as do retinoblastoma and Wilms tumor. The relevant locus must be located on the telomeric side of the D1S1 locus on the short arm of chromosome 3.

Carcinoma, Renal Cell↗
PubMed1988

Drosophila homolog of the murine Int-1 protooncogene.

We have isolated phage clones from Drosophila melanogaster genomic and cDNA libraries containing a sequence homologous to the murine Int-1 protooncogene. The Drosophila gene is represented by a single locus at position 28A1-2 on chromosome 2. The gene is expressed as a 2.9-kilobase-long polyadenylylated mRNA in embryo, larval, and pupal stages. It is hardly detectable in adult flies. The longest open reading frame of the cDNA clone corresponds to a protein 469 amino acids long. Alignment of the predicted amino acid sequences shows that the Drosophila protein is 86 amino acids longer than its murine counterpart. In spite of the difference in length, the two proteins are highly conserved with an overall sequence homology of 54%. Both Drosophila and murine Int-1 proteins begin with a hydrophobic leader sequence and contain cysteine residues and sites for glycosylation (four in the murine protein and one in the Drosophila protein) in conserved positions, suggesting that they play important functional roles.

Amino Acid Sequence↗
PubMed1988

Structure and expression of B-myc, a new member of the myc gene family.

The myc family of genes contains five functional members. We describe the cloning of a new member of the myc family from rat genomic and cDNA libraries, designated B-myc. A fragment of cloned B-myc was used to map the corresponding rat locus by Southern blotting of DNA prepared from rat X mouse somatic cell hybrids. B-myc mapped to rat chromosome 3. We have previously mapped the c-myc to rat chromosome 7 (J. Sümegi, J. Spira, H. Bazin, J. Szpirer, G. Levan, and G. Klein, Nature [London] 306:497-498, 1983) and N-myc and L-myc to rat chromosomes 6 and 5, respectively (S. Ingvarsson, C. Asker, Z. Wirschubsky, J. Szpirer, G. Levan, G. Klein, and J. Sümegi, Somat. Cell Mol. Genet. 13:335-339, 1987). A partial sequence of B-myc had extensive sequence homology to the c-myc protein-coding region, and the detection of intron homology further indicated that these two genes are closely related. The DNA regions conserved among the myc family members, designated myc boxes, were highly conserved between c-myc and B-myc. A lower degree of homology was detected in other parts of the coding region in c-myc and B-myc not present in N-myc and L-myc. A 1.3-kilobase B-myc-specific mRNA was detected in most rat tissues, with the highest expression in the brain. This resembled the expression pattern of c-myc, although at different relative levels, and was in contrast to the more tissue-specific expression of N-myc and L-myc. B-myc was expressed at uniformly high levels in all fetal tissues and during subsequent postnatal development, in contrast to the stage-specific expression of c-myc.

Animals↗
PubMed1988

Chromosome localization and expression pattern of Lmyc and Bmyc in murine embryonal carcinoma cells.

Using Southern blot analysis of DNA from mouse-hamster somatic cell hybrids, we have mapped Lmyc and Bmyc, two members of the myc family of genes, to mouse chromosomes 4 and 2, respectively. Furthermore, we have compared the regulation of Lmyc and Bmyc expression under different growth conditions and during in vitro differentiation of the murine EC line F9 and considered the findings in relation to our previous studies on Nmyc and c-myc expression in the same line (Sejersen et al., 1987). Lmyc was down-regulated at an early stage of visceral endoderm differentiation, similarly to c-myc and Nmyc, while Bmyc was expressed at a constant low level at all stages. Lmyc, but not c-myc and Nmyc, was upregulated in terminally differentiated visceral endoderm cells. Inhibition of protein synthesis by cycloheximide for 4 h induced a 70% increase in Lmyc and 30% increase in Bmyc transcript levels, indicating that the expression of these genes is negatively regulated by a short-lived protein. Mitogenic stimulation with insulin and transferrin did not affect Lmyc and Bmyc mRNA levels. Lmyc transcripts have a half life of 30 min, whereas the Bmyc transcript is highly stable, with a half life of 6 h. The half-lives of the c-myc and Nmyc transcripts have been estimated previously as 40 and 130 min, respectively.

Animals↗
PubMed1988

Elevated expression of c-myc and N-myc produces distinct changes in nuclear fine structure and chromatin organization.

The proto-oncogenes c-myc and N-myc encode nuclear phosphoproteins with unknown function. Here, c-myc or N-myc, or hybrid constructs of the two, were transfected into fibroblastic cells (CV-1) using SV40-based high expression vectors. The cells were studied by indirect immunofluorescence microscopy and transmission electron microscopy to determine the localization of the two myc proteins within the nucleus and their influence on nuclear fine structure and chromatin organization. In c-myc transfected cells the overproduced protein product accumulated in large amorphous globules that displaced the normal chromatin and did not stain for DNA. In N-myc transfected cells condensed chromatin loops were formed. They were attached to the nuclear envelope and by traction in the latter they may have contributed to give the nucleus its irregular shape in these cells. During mitosis the chromatin loops persisted as clearly identifiable entities within the chromosomes, suggesting a rigid conformation that did not allow normal chromosome packaging. These findings suggest that the c-myc and N-myc proteins bind to different structures and may have different functions. Observations on cells transfected with hybrid constructs indicated that both the second and third exon of c-myc were required to yield a product that behaved like the c-myc protein. In contrast, domains encoded by the second exon of N-myc were sufficient to give rise to a product that morphologically behaved like the N-myc protein.

Animals↗