Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated a partial cDNA encoding the cystic fibrosis transmembrane conductance regulator (CFTR) in the rat. This cDNA hybridizes to a 6.1-kb RNA transcript from the human T84 epithelial cell line and a similarly sized transcript from the rat parotid gland. The nucleotide sequence of this cDNA shows 80.5% identity to the human CFTR cDNA sequence, and the deduced amino acid sequence of rat CFTR shows 75.5% identity to the amino acid sequence of human CFTR. We have used this cDNA to map the location of the gene encoding CFTR to rat chromosome 4. This result places CFTR within a syntenic group on rat chromosome 4 and on human chromosome 7 that includes the genes encoding interleukin 6 (IL6), erythropoietin (EPO), P-glycoprotein 1 (PGY1), and T cell receptor beta chain (TCRB). This group is divided between chromosomes 5 and 6 in the mouse. Mapping of CFTR to rat chromosome 4 shows that this syntenic group has been divided in the mouse lineage during the past 15 million years and further localizes that breakpoint to a sequence homologous to the human chromosome 7q21.1 and 7q32 region. Similarly, a group of five genes, CFTR, TCRB, HOX1, parathyroid hormone-like hormone (PTHLH), and Kirsten rat sarcoma 2 viral (v-Ki-ras2) oncogene homolog (KRAS2), is syntenic on rat chromosome 4 and mouse chromosome 6, but is divided between human chromosomes 7 and 12. These data suggest that the ancestral mammalian chromosome appeared as the present day rat chromosome 4, with all six genes grouped together, and that chromosomal breakages have occurred in the mouse and human lineages since the mammalian divergence.
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PMID:Localization of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) in the rat to chromosome 4 and implications for the evolution of mammalian chromosomes. 128 91

Four murine cellular tumor models expressing various combinations of oncogenes (SV40 large T and v-Ha-ras, SV40 large T and v-src, SV40 large T and neu, adenovirus EIA and v-Ha-ras) induce sarcoma when they are inoculated s.c. into the DBA/2 syngenic mice. The metastatic patterns, distribution and fate of these tumor cells transplanted by two different routes into syngenic DBA/2 mice have been studied. All the tumor cell lines except EIA-ras, induce massive overt artificial metastases principally in the lung after i.v. injection. In s.c. tumor-bearing mice, a few resting cells colonize the lung as micrometastases. When removed from this tissue context and injected s.c. these cells regain their proliferative potential and grow as local tumors which again give rise to occult pulmonary micrometastases.
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PMID:Metastatic phenotype of murine tumor cells expressing different cooperating oncogenes. 131 11

Replicate sets of cultures of mouse and of human cells were exposed to cyclic, sine wave, 60-Hz rotating magnetic fields of 1.0 Gs (1 Gs [symbol: see text] 0.1 mT) for 24-, 48-, or 72-h periods. Total RNA extracted from unexposed control and from magnetic field exposed cells was dot blot hybridized to a number of oncogene probes (including v-myc, v-fos, v-raf, and v-Ha-ras), a probe for 3611 murine sarcoma virus, a probe for the 70,000 dalton heat shock protein (hsp70), and a probe for the long terminal repeat sequence of mouse mammary tumor virus. Comparisons of levels of RNA in unexposed and magnetic field exposed cells measured by densitometer readings of resulting autoradiographs revealed no significant increases or decreases in RNA levels in magnetic field exposed cells with the seven probes tested.
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PMID:Expression of gene-specific RNA in cultured cells exposed to rotating 60-Hz magnetic fields. 132 60

The raf genes encode a family of cytoplasmic proteins with intrinsic protein-serine/threonine kinase activity. The c-raf gene is the cellular homolog of v-raf, the transforming gene of murine sarcoma virus 3611. The constitutive kinase activity of the v-Raf protein has been implicated in transformation and mitogenesis. The activity of Raf-1, the protein product of the c-raf gene, is normally suppressed by a regulatory N-terminal domain. Activation of various tyrosine-kinase growth factor receptors results in activation of Raf-1 and its hyperphosphorylation. Further, Raf-1 has been shown to act either downstream or independently of the p21ras protein, as indicated by experiments involving microinjection of anti-Ras antibodies. To investigate the potential role of p21ras in the activation of Raf-1 by tyrosine kinases, we have used the baculovirus/Sf9 cell system to overproduce various wild-type and mutant forms of pp60src, p21ras, and Raf-1 proteins. We show that either pp60v-src or p21c-ras can independently activate the autokinase activity of Raf-1, but only to a limited extent. Surprisingly, both pp60v-src and p21c-ras are required to fully activate Raf-1. Analysis of the Raf-1 autokinase activity in vitro shows that Raf-1 autophosphorylation sites are distributed equally on serine and threonine residues. When Raf-1 is analyzed by immunoblotting, as previously reported for mammalian cell experiments, a marked increase in the apparent molecular weight of Raf-1 is seen only when it is coexpressed with both pp60v-src and p21ras.
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PMID:Both p21ras and pp60v-src are required, but neither alone is sufficient, to activate the Raf-1 kinase. 137 95

In embryogenesis, ovarian surface epithelial cells and ovarian granulosa cells arise through divergent differentiation from a common mesenchymal precursor, the urogenital ridge. In the adult rat, ovarian surface epithelial cells are nonsteroidogenic and keratin positive, while ovarian granulosa cells are steroidogenic and keratin negative. In culture, Kirsten murine sarcoma virus-transformed, tumorigenic ovarian surface epithelial cells continued to express keratin but also became steroidogenic. Transformed ovarian granulosa cells remained steroidogenic but also acquired keratins. Mesodermally derived cells from other sources did not show these differentiation-related changes in response to transformation. The results suggest that v-ras oncogenes may cause the reversion of adult, developmentally related cells to the phenotype of a common, multipotential precursor. They also demonstrate the capacity of v-ras to either induce or reduce the same differentiated characteristic, depending on the developmental history of the target cells.
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PMID:Reversal of divergent differentiation by ras oncogene-mediated transformation. 137 24

We utilized confocal laser scanning microscopy to examine the localization of fibronectin deposition in cultures of human endometrial stromal cells. We found that fibronectin in normal human endometrial stromal cell cultures was both intracellular, occurring in rough endoplasmic reticulum and in perinuclear regions, and extracellular, occurring diffusely over the entire cell surface. Endometrial stromal cells were transfected with a plasmid containing an origin-defective Simian Virus 40 (SV40) which codes for a temperature-sensitive large T antigen. When these cells were placed under temperature-restrictive conditions for large T-antigen function, they exhibited staining patterns similar to normal endometrial cells. Fibronectin deposition in cultures of partially or fully transformed endometrial cells was not intracellular as in normal cells, but was localized primarily between cells. Cells expressing the SV40 large T antigen deposited fibronectin mainly in parallel clumps between cells. Cells expressing both the SV40 large T antigen and the EJ ras oncogene, at high cell density, displayed networks of fibronectin arranged in matrix-like patterns between cells. The malignant cell line examined, sarcoma cells, also exhibited fibronectin networks between cells. Cell density affected fibronectin deposition in endometrial stromal cells expressing the EJ ras oncogene. At low density, cells expressing the SV40 large T antigen and the EJ ras oncogene displayed diffuse fibronectin patterns and, at high density, these cells formed colonies with networks of fibronectin between cells.
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PMID:Effects of the SV40 large T antigen and EJ ras oncogene on fibronectin localization in human endometrial cells as viewed by confocal laser scanning microscopy. 154 49

We have previously characterized human smooth muscle myosin light chain (MLC)-2 isoform by complementary DNA cloning and have shown that this isoform is expressed in a number of nonmuscle cells such as fibroblast cells. In this report, we show that when human osteosarcoma derived clonal cells (TE 85 clone F-5) (HOS), which are immortalized and nontumorigenic, undergo transformation following infection by Kirsten murine sarcoma virus (K-HOS) or by a chemical carcinogen [N-methyl-N-nitro-N-nitrosoguanidine (MNNG-HOS)], the smooth muscle MLC-2 mRNA is repressed. Revertants of transformed K-HOS cells (K-HOS312H) show normal levels of smooth muscle MLC-2 mRNA. Transformation of HOS cells by Ha-ras oncogene sequences, either by retroviral infection or by transfection followed by selection for tumorigenic cells in nude mice, results in complete repression of smooth muscle MLC-2 mRNA level. Treatment of HOS cells with tumor promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, results in repression of smooth muscle MLC-2 mRNA. Smooth muscle MLC-2 mRNA level is repressed in many, but not all, transformed cell lines, suggesting that it is not an indirect consequence of transformation but is specific to the agent that brings about transformation. HOS cells synthesize three MLC-2 protein species resolved by the two-dimensional gel electrophoretic system. The identity of the smooth muscle MLC-2 isoform was established by coelectrophoresis of the in vitro synthesized MLC-2 protein corresponding to the cloned complementary DNA in the two-dimensional gel system along with total [35S]methionine labeled HOS cell proteins. Quantitative analysis of MLC-2 isoforms in different HOS cells indicates that the synthesis of smooth muscle MLC-2 isoform is specifically repressed to an undetectable level in ras transformed and MNNG transformed cells and also following treatment with 12-O-tetradecanoylphorbol-13-acetate.
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PMID:Human smooth muscle myosin light chain-2 gene expression is repressed in ras transformed fibroblast cells. 159 78

Screening for gene(s) homologous to v-Ha-ras (Harvey rat sarcoma viral ras gene) in the basidiomycete, Lentinus edodes, resulted in the isolation of a novel gene (designated priA), in addition to a ras gene homologue [Hori et al., Gene 105 (1991) 91-96]. The priA gene has a coding capacity of 258 amino acids (aa) interrupted by two short putative introns. The 5'-upstream region of priA contains GGGCGG box, CCAAT box, TATAAA box and CT sequence elements in 5'----3' order. One transcription start point (tsp) was located 10 nucleotides upstream from a TATAAA box and another tsp just in a CT sequence. The deduced PRIA protein (26.7 kDa), rich in Ser (42 residues), Pro (29 residues) and Thr (27 residues), contained different types of putative zinc-binding motifs. It initiated with a hydrophobic aa sequence and terminated with the unique sequence, Cys-Aaa-Aaa-Xaa (where Aaa is aliphatic aa and Xaa is any aa), implying an association with the inner membrane surface via acylation of the Cys residue. The priA gene expression was found to be developmentally regulated with primordia/immature fruiting bodies having much higher levels of priA transcript. Preprimordial mycelia and mature fruiting bodies, however, contain very low levels of priA transcript. The priA gene may play a role during the beginning of fruiting.
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PMID:Isolation and sequence of a developmentally regulated putative novel gene, priA, from the basidiomycete Lentinus edodes. 160 1

To identify molecules on the cell surface involved in negative growth regulation, we assumed that their amounts would be reduced after malignant transformation. We analyzed several proteins by fluorescence-activated cell sorter in mouse NIH 3T3 and its transformed cell lines. Surprisingly, the amount of Thy-1, a cell surface glycoprotein anchored in the cell membrane by a glycophosphatidyl inositol linkage, was significantly decreased in the transformed NIH 3T3 lines, especially in ras-transformed NIH 3T3 lines. The malignant properties of clones of NIH 3T3 transformed by Kirsten murine sarcoma virus have a good correlation not only with the high amount of RAS proteins but also inversely with the amount of Thy-1. NIH 3T3 subpopulations lacking Thy-1 exhibit more susceptibility to the induction of colony-forming ability in soft agar by Kirsten murine sarcoma virus than the Thy-1-positive populations. Finally the transfection of Thy-1 complementary DNA to the ras-transformed NIH 3T3 significantly inhibits the colony formation in soft agar as well as the tumor formation in nude mice. Our results suggest that Thy-1 has negative effects on the anchorage-independent growth of ras-transformed NIH 3T3 cells.
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PMID:Thy-1 as a negative growth regulator in ras-transformed mouse fibroblasts. 167 Sep 96

After mixed infection, up to half of related retroviruses are recombinants. During infection, retroviral RNA genomes are first converted to complementary DNA (cDNA) and then to double-stranded DNA. Thus recombination could occur during reverse transcription, by RNA template switching, or after reverse transcription, by breakage and reunion of DNA. It has not been possible to distinguish between these two potential mechanisms of recombination because both single-stranded cDNA and double-stranded proviral DNA exist in infected cells during the eclipse period. Therefore we have analyzed for recombinant molecules among cDNA products transcribed in vitro from RNA of disrupted virions. Since recombinants from allelic parents can only be distinguished from parental genomes by point mutations, we have examined the cDNAs from virions with distinct genetic structures for recombinant-specific size and sequence markers. The parents share a common internal allele that allows homology-directed recombination, but each contains specific flanking sequences. One parent is a synthetically altered Harvey murine sarcoma virus RNA that lacks a retroviral 3' terminus but carries a Moloney murine retrovirus-derived envelope gene (env) fragment 3' of its transforming ras gene. The other parent is intact Moloney virus. Using a Harvey-specific 5' primer and a Moloney-specific 3' primer, we have found recombinant cDNAs with the polymerase chain reaction, proving directly that retroviruses can recombine during reverse transcription unassisted by cellular enzymes, probably by template switching during cDNA synthesis. The recombinants that were obtained in vitro were identical with those obtained in parallel experiments in vivo.
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PMID:Retroviral recombination during reverse transcription. 169 Apr 24


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