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Biomedical subjects

G Levan

Publications and source records attributed to G Levan.

At least 145 records · Page 8Linked to original sources
PubMed1988

Assignment of gene for coagulation factor V to chromosome 1 in man and to chromosome 13 in rat.

Two different factor V cDNA fragments were used as hydridization probes in the chromosomal assignment of the human and rat factor V genes. A 1.6-kb EcoRI fragment was used as a hybridization probe to analyze a panel of human-rodent somatic cell hybrids. Cosegregation of factor V specific DNA restriction fragments with human chromosome 1 was observed. In addition, a panel of rat-mouse somatic cell hybrids was analyzed with another human factor V cDNA probe to localize the gene for rat coagulation factor V. In the rat, the gene for coagulation factor V was found to be located in chromosome 13. This is the first gene in the rat to be localized to chromosome 13.

Animals↗
PubMed1988

Tumorigenicity of SEWA murine cells correlates with degree of c-myc amplification.

Previous studies have shown that cells of the SEWA mouse tumor contain amplified copies of the proto-oncogene c-myc in the aberrant chromosomal structures of double minutes (DMs), homogeneously staining regions (HSRs) and C-bandless chromosomes (CMs). DMs, and to a lesser degree CMs, tend to disappear from the cells grown in vitro and again reappear after transfer back in vivo, as if DNA amplification confers a growth advantage upon the tumor cells. We have now isolated five in vitro clones that exhibit different degrees of c-myc amplification. When we inoculated cells of the different clones into compatible hosts, we found that there was a positive correlation between degree of c-myc amplification, level of c-myc RNA, and tumorigenicity. Our results lend further support to the idea that gene amplification contributes to the higher malignant phenotype, and to progression of tumors.

Animals↗
PubMed1987

Novel cytogenetic expression of gene amplification in actinomycin D-resistant somatic cell hybrids: transfer of resistance by centric chromatin bodies.

SEWATC13 mouse cells, resistant to 0.1 microgram/ml of actinomycin D (AMD), were fused to AMD-sensitive cells of the Chinese hamster ovary cell line (CHO). Twenty-two hybrid clones were isolated and put into serial culture in the selective medium. Unexpectedly, identifiable mouse chromosomes were found only in one of the hybrids. All the others had only hamster chromosomes and, in addition, numerous chromatin bodies (CBs), mostly small and irregularly shaped, but also larger, more chromosome-like ones. The CBs were distinctly C-band positive and a mouse satellite probe hybridized strongly to them. The AMD resistance of the murine parental cells had previously been attributed to gene amplification in two large homogeneously staining regions (HSR-AMD1 and 2). They were not observed in the hybrid cells but had supposedly reappeared in the guise of the CBs. It was established by Southern DNA blot analysis that amplified DNA sequences, localized to the HSR-AMD1 and 2 of the SEWA parent were present in multiple copies in the hybrids. It was also established by in situ hybridization that they were located in the CBs. Unlike double minutes (DMs) the CBs were all centric.

Animals↗
PubMed1987

All six rat gamma-crystallin genes are located on chromosome 9.

The rat genome contains six genes for the lens-specific gamma-crystallins. Five of these genes are clustered; the location of the sixth gene is not known. To determine whether the sixth gene is located on the same chromosome as the gamma-crystallin gene cluster, a panel of mouse-rat hybrid cell lines, segregating rat chromosomes, was screened for the presence of gamma-crystallin sequences. We show here that the hybrid cell lines contain either all rat gamma-crystallin genes or none, indicating that all six genes map to the same chromosome. The presence of rat gamma-crystallin sequences in the hybrid cell lines was concordant only with the presence of rat chromosome 9, which therefore contains the rat gamma-crystallin genes.

Animals↗
PubMed1987

Localization of the multidrug resistance-associated 170 kDa P-glycoprotein gene to mouse chromosome 5 and to homogeneously staining regions in multidrug-resistant mouse cells by in situ hybridization.

This report describes the localization of the 170 kDa P-glycoprotein gene(s) to mouse chromosome 5, subbands A2 or A3. Overproduction of P-glycoprotein is associated with multidrug resistance (MDR). MDR cell lines derived from the SEWA mouse tumor carry multiple copies of the P-glycoprotein gene. These were found to reside in homogeneously staining regions, situated in different locations in different sublines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1987

The rat MIS1/Pvt-1 locus is syntenic with MYC on chromosome 7.

Mouse Pvt-1 and rat MIS1 are frequent proviral integration sites in retrovirally induced lymphomas. The Pvt-1 locus is also involved in mouse plasmacytoma (6;15) and in the variant Burkitt lymphoma (2;8) translocations. We show that the Pvt-1/MIS1 locus is syntenic with MYC on rat chromosome 7. This is consistent with a postulate of close linkage and, possibly, a functional relationship between the MYC protooncogene and the MIS1/Pvt-1 locus.

Animals↗
PubMed1986

Localization of the rat immunoglobulin heavy chain locus to chromosome 6.

We have previously used rat/mouse somatic cell hybrids to localize the rat c-myc gene to chromosome 7 (Sümegi et al. 1983) and the rat immunoglobulin kappa locus to chromosome 4 (Perlmann et al. 1985). We now report that by utilizing rat/mouse somatic cell hybrids, we have localized the rat immunoglobulin heavy chain locus to chromosome 6.

Animals↗
PubMed1986

The related genes encoding growth hormone and prolactin have been dispersed to chromosomes 10 and 17 in the rat.

We have assigned the rat GH gene to chromosome 10 and the rat PRL gene to chromosome 17. DNA from a series of mouse BWTG3 x rat hepatocyte somatic cell hybrids, each of which has retained a unique complement of rat chromosomes, was analyzed for the presence of rat GH and PRL genomic fragments by Southern blotting. Radiolabeled complementary DNAs (cDNAs) encoding rat GH and rat PRL were used as molecular probes. Based upon these assignments, we conclude that the evolutionarily related GH and PRL genes have been dispersed to different chromosomes in rat as in man.

Animals↗
PubMed1985

Assignment of three rat cellular RAS oncogenes to chromosomes 1, 4, and X.

Mouse hepatoma-rat hepatocyte hybrids that segregate rat chromosomes were used to determine the chromosomal localization of rat cellular RAS genes. The cellular KRAS gene, homologous to the Kirsten sarcoma virus oncogene was mapped to rat chromosome 4, a chromosome that is often present in three copies in rat neurogenic tumor cells and transformed glial cells. The rat cellular HRAS-1 gene, homologous to the Harvey sarcoma virus oncogene was assigned to chromosome 1, whereas its intron-less counterpart HRAS-2 was mapped to the X chromosome. Since the human HRAS-2 also resides on the X chromosome, it appears that the cellular HRAS-2 gene (or pseudogene) conserved its chromosomal localization during mammalian evolution.

Animals↗
PubMed1985

Pleiotropic drug resistance and gene amplification in a SEWA mouse tumor cell line. Complex relations revealed by drug uptake data, and lipid and protein analysis.

SEWA mouse lines resistant to actinomycin D (AMD) or vincristine (VCR) exhibit the pleiotropic drug resistance (PDR) phenotype, and express a low-MW protein (p21) and numerous double minutes (DM). In drug uptake studies these lines were compared with the non-resistant parental line and with a methotrexate (MTX)-resistant line, not exhibiting PDR. On treatment with labelled AMD or VCR the two PDR lines displayed a highly reduced intracellular content of drug, whereas uptake of MTX was unchanged. Uptake of AMD was shown to be temperature-dependent. The MTX-resistant line did not exhibit any significant change in AMD or VCR uptake. Other workers have emphasized the role of a high-MW glycoprotein in the development of PDR. A search for a similar glycoprotein in our cells was unsuccessful. Since all indications point to membrane factors being important in the development of PDR, the lines were also subjected to lipid analysis. Compared with control cells distinct differences were detected in the lipid composition of all resistant lines (including the MTX-resistant line). In the course of our experiments, the DM in our most AMD-resistant line were replaced by two homogeneously staining regions (HSR). Simultaneously, the overproduction of p21 ceased, but the PDR phenotype persisted. This event tends to implicate a minor role for the p21 protein in PDR, but similar transitions from DM to HSR in other AMD-resistant SEWA lines were not accompanied by a decrease in p21 over-production. Our data point to a complex genetic control of multi-drug resistance.

Animals↗
PubMed1985

Cellular DNA regions involved in the induction of rat thymic lymphomas (Mlvi-1, Mlvi-2, Mlvi-3, and c-myc) represent independent loci as determined by their chromosomal map location in the rat.

The induction of thymic lymphomas by Moloney murine leukemia virus in the rat is linked to provirus integration in at least four independent cellular DNA regions (Mlvi-1, Mlvi-2, Mlvi-3, and c-myc). Because sequences homologous to at least three of these regions (Mlvi-1, Mlvi-2, and c-myc) map to chromosome 15 in the mouse, the question was raised whether they are closely linked in the rat genome and whether provirus integration in any one of these regions affects the same functional domain in rat DNA. In this study, we identified the chromosomal map location of Mlvi-1, Mlvi-2, and Mlvi-3 in the rat by using mouse-rat somatic cell hybrids that lose the rat chromosomes. The results showed that Mlvi-1 maps similarly to c-myc to chromosome 7, and Mlvi-2 maps to chromosome 2. Mlvi-3 probably maps to chromosome 15. We conclude that Mlvi-1, Mlvi-2, and Mlvi-3 are separate and independent genetic loci. Although Mlvi-1 and c-myc map to the same chromosome, they are not related, as determined by hybridization and restriction endonuclease mapping. The chromosomal map location of Mlvi-1 to chromosome 7 and Mlvi-2 to chromosome 2 is interesting, since chromosomal aberrations involving these two chromosomes are reproducibly observed in rat neoplasias induced by a variety of agents.

Animals↗