Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The abilities of malignant tumor cells to bind and migrate through basement membranes are important steps in invasion and metastasis. Malignant tumor cells would therefore be expected to express receptors on their surfaces for basement membrane and stromal components, such as collagens, laminin, and fibronectin, although the pattern of expression of these receptors on the malignant cells may be different from that on their normal progenitors. We report here that chemically transformed tumorigenic human cells express an altered pattern of integrin receptors on their cell surfaces as compared with their untransformed nontumorigenic counterparts. Specifically, N-methyl-N'-nitro-N-nitrosoguanidine transformation of HOS cells into highly tumorigenic cells results in a significant specific increase in the expression of (in descending order of level of cell surface expression) the integrins alpha 6/beta 1, alpha 2/beta 1, and alpha 1/beta 1, which are receptors for laminin, collagens, and collagen type IV and laminin, respectively. The level of expression of two fibronectin receptor integrins, alpha 5/beta 1 and alpha 3/beta 1, are, however, unaltered, whereas the level of expression of vitronectin receptor integrin, alpha v/beta 3, is drastically reduced on the transformed cells. Consistent with the increased expression of laminin and collagen receptors and the decreased expression of vitronectin receptors on the transformed cells, these cells attached three- to fivefold more strongly to laminin and collagen but attached very poorly to vitronectin. The MNNG-HOS cells were also found to have a greater potential for invasion through reconstituted basement membrane, matrigel, the major components of which are laminin and type IV collagen. The invasion of both the HOS and MNNG-HOS cells was inhibited 45-50% by a polyclonal anti-fibronectin receptor antibody. However, although the invasion of HOS cells could be inhibited up to 75% by an anti-alpha 6 monoclonal antibody, a similar concentration of this antibody had no effect on the alpha 6-overproducing MNNG-HOS cells. A fivefold higher concentration of this antibody did result in partial inhibition of MNNG-HOS invasion. These data indicate a critical role for the alpha 6/beta 1 laminin receptor in the invasion of these cells through basement membranes and demonstrate that chemical transformation of nontumorigenic human cells to highly tumorigenic cells is associated with an altered pattern of integrin expression which may play a direct role in the increased capacity of these cells to bind and invade through basement membranes.
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PMID:Alterations in integrin receptor expression on chemically transformed human cells: specific enhancement of laminin and collagen receptor complexes. 168 58

The presence and functions of steroid receptors were evaluated in three human osteosarcoma cell lines (OS1 = SA OS; OS2 = HOS TE 85, and OS3 = MNNG HOS TE 85). The human breast cancer cell line MCF-7 was used as internal control for oestrogen receptors (E2R). High and low affinity sites were characterised. The high affinity sites had a similar dissociation constant in all four cell lines. In contrast, the number of sites per cell was higher in MCF-7 cells. E2 did not significantly modify the number of progesterone receptors (PgR) per cell in any of the osteosarcoma lines. As expected, E2 increased the number of PgR sites per MCF-7 cell. 4-hydroxytamoxifen decreased the growth of MCF-7 cells only. OS1 and OS2 were sensitive only to the highest concentration tested, which produces only non-specific cytotoxic effects. Thus E2R and PgR were found in osteoblast-like cells, but the function of E2R in such cells remains unknown.
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PMID:Steroid receptors in human osteoblast-like cells. 214 99

We have previously shown that two alleles of the MET locus are independently rearranged in the chemically-treated human cell line MNNG-HOS. One allele is the TPR-MET oncogene which was activated by fusion of the MET locus on chromosome 7 with the TPR locus on chromosome 1. The second allele is found on a der(7)t(1;7)(q23;q32) chromosome and is characterized by a deletion of the amino-terminus of the MET extracellular ligand binding domain. Here we present a pulsed field gel electrophoresis analysis which reveals that the two MET allele rearrangements in MNNG-HOS cells are more complex than originally thought. The breakpoint in MET on der(7) has been molecularly cloned and, unexpectedly, we found that rearrangement in this allele involves sequences derived from chromosome 2. Moreover, the rearrangement producing der(7) involves an inversion of the MET locus or a more complex alteration. Analysis of hybrid cells containing TPR-MET demonstrated that both the upstream and downstream portions of MET are conserved in this rearrangement and that oncogene activation occurred by an insertion of TPR sequences into the MET locus. These findings illustrate that when examined at the molecular level some chromosome abnormalities can be extremely complex and, thus, are of limited value in gene mapping studies.
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PMID:Analysis by pulsed field gel electrophoresis reveals complex rearrangements in two MET alleles in a chemically-treated human cell line, MNNG-HOS. 225 Sep 12

The MET oncogene, present in the MNNG-HOS chemically transformed human cell line, is activated by a gene fusion involving sequences from chromosome 1 and chromosome 7. Activated MET can act as a dominant selectable marker for chromosome-mediated gene transfer, and several transfectant cell lines have been established using this technique. Analysis of the transgenomes within these cell lines indicates that MET activation is not simply due to a chromosome translocation, but may involve an interstitial insertion of DNA from chromosome 1, into chromosome 7, probably associated with other rearrangements. Pulse field gel analysis of two transfectants indicates that, despite the presence of complex rearrangements close to MET, chromosome 7 sequences are grossly intact over a 1-Mb region thought to contain the gene defective in cystic fibrosis.
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PMID:Analysis of the transgenome of MET transfectant cell lines reveals that MET activation is accompanied by an interstitial insertion. 230 48

Interferons potentiate the cytotoxic effects of certain antineoplastic drugs on human tumor cells both in vitro and in vivo, although the mechanism of interferon's synergistic action is unknown. Interferon may act by modulating the expression of DNA repair activity in cells. To test this hypothesis, we maintained parallel cultures of normal O6-methylguanine repair-proficient human fibroblasts and tumor cells, or RSV-and SV40-transformed repair-deficient Mer- human fibroblasts in medium containing 0, 100, 500 or 680 U/ml human interferon alpha or beta; after 1-10 weeks, cultures were challenged with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, CAS: 70-25-7) and assayed for colony-forming ability. Based on the dose at 99% lethality, MNNG cytotoxicity was potentiated from 1.3- to 9-fold in interferon-treated cultures, compared with control cultures (no interferon). A significant potentiation was observed both with Mer+ normal fibroblasts (KD strain) and tumor cells (HOS) and with Mer- SV40-transformed fibroblasts (IMR90-830 and GM638) as well as with RSV-transformed cells (RHOS). However, the degree of potentiation was greater in Mer- virus-transformed cells than in Mer+ cells. The greatest effects were observed with Mer- IMR90-830 cells (5- to 9-fold reduction of dose at 99% lethality). Therefore, because the Mer+ phenotype is not required in order for HuIFNs to sensitize cells to killing by MNNG, interferon does not act by modulating O6-methylguanine repair. However, the effect of interferon on O6-methylguanine-DNA methyltransferase levels and on DNA excision repair should be examined in future experiments.
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PMID:Synergistic killing of virus-transformed human cells with interferon and N-methyl-N'-nitro-N-nitrosoguanidine. 246 81

We have found that two alleles of the MET locus are rearranged in the human cell line MNNG-HOS. One allele is the previously characterized TPR-MET oncogene and the other is found on a der(7)t(1;7)(q23;q32) marker chromosome. These data and in situ chromosomal hybridization analysis would indicate that MET and, therefore, the cystic fibrosis locus are located at bands q31-q32 on human chromosome 7. Using somatic cell hybrids, we show that the chromosome containing the TPR-MET oncogene is grossly rearranged and contains both the upstream and downstream portions of the MET protooncogene locus. These results demonstrate that the TPR-MET oncogene rearrangement involving chromosomes 1 and 7 is either due to an insertion of TPR sequences into the MET locus or is more complex. We also show that the upstream MET protooncogene locus is deleted on der(7), while the downstream portion is retained. We cannot exclude that this is due to an interstitial chromosomal deletion or to a more complex rearrangement, but if MET maps at the breakpoint in der(7), then the 3' end of the MET transcription unit should be oriented towards the centromere. We also show that other DNA restriction fragment length polymorphism markers tightly linked with the inheritance of cystic fibrosis are deleted on der(7).
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PMID:Two rearranged MET alleles in MNNG-HOS cells reveal the orientation of MET on chromosome 7 to other markers tightly linked to the cystic fibrosis locus. 328 34

The DNA probes met and pJ3.11 are derived from loci on chromosome seven that are closely linked to, and probably flanking, the gene mutation causing cystic fibrosis (CF). We have shown that mitotic chromosomes from the cell line MNNG-HOS, which contains an activated met oncogene, can induce morphological transformation of mouse NIH-3T3 cells. Southern analysis of isolated transfectant cell lines with cloned dispersed repetitive human DNA sequences as probes demonstrated that several lines of transformed NIH 3T3 cells had stabley incorporated large segments of chromosome seven DNA. Southern blot analysis also demonstrated the presence of met, pJ3.11 and several other single copy sequences that had been previously localised to chromosome 7 within the transgenomes. In this way a further four genetic markers were shown to be physically linked to met, and thus to CF. These probes may prove useful in confirming the order of loci around CF and in the prenatal diagnosis of this common autosomal recessive disease.
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PMID:Chromosome mediated gene transfer of six DNA markers linked to the cystic fibrosis locus on human chromosome seven. 376 3

In this study it is demonstrated that the activated met gene, which was originally detected in the MNNG-HOS chemically transformed human cell line, is a chimeric gene formed by the joining together of two distinct regions of DNA. Rearrangement of cellular DNA in MNNG-HOS cells was demonstrated by Southern analyses, which showed that the MNNG-HOS cell line contained unique met-related DNA fragments that were not detected in the parental cell line, HOS. Chromosomal localization using a series of rodent-human hybrid cell lines showed that the 5' end of the activated met gene is derived from human chromosome 1, in contrast to the 3' end of met which has been previously localized to human chromosome 7. The chimeric gene is transcribed to produce a 5-kb mRNA that is encoded both by regions of the gene derived from chromosome 1 and by regions of the gene derived from chromosome 7. Karyotype analysis of HOS and MNNG-HOS cells has identified several marker chromosomes that involve translocations of chromosomes 1 and 7. The possible location of the activated met locus within these rearranged chromosomes is discussed.
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PMID:Activation of the met oncogene in the human MNNG-HOS cell line involves a chromosomal rearrangement. 377 99

Two sets of abundant cytoplasmic transformation-specific polypeptides, p788/p789 and p219/p220, have been identified by comparing in vitro-transformed human fibroblasts with diploid human fibroblasts. These polypeptides are also expressed by the human fibrosarcoma and osteosarcoma cell lines HT1080 the human fibrosarcoma and osteosarcoma cell lines HT1080 and HOS, respectively. HOS cells, however, synthesize only one of the two electrophoretic forms of each marker set, p789 and p219, at greatly reduced rates compared to the rates of synthesis found for HT1080 cells and the in vitro-transformed cell lines. Induction of expression of these neoplastic marker polypeptides is independent of the activation of a transforming gene that will induce focus formation in confluent mouse 3T3 cell monolayers. Activation of the met oncogene in MNNG-HOS cells and simultaneous elevation of tumorigenic potential did not lead to a significant change in the rate of the 600 most abundant polypeptide species with the exception of one of the two cytoplasmic actin polypeptides. While the normal ratio of beta-to gamma-actin which is approximately 2:1 was expressed in "untransformed" HOS cells, MNNG-HOS cells synthesized 50% less beta-actin resulting in a 1:1 ratio of beta-actin to gamma-actin. Our finding here, together with our previous characterization of the human beta-actin gene, leads us to predict that one of two functional beta-actin genes expressed in HOS cells has been inactivated in MNNG-HOS cells by either a regulatory or structural gene mutation.
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PMID:Expression of neoplasia-related proteins of chemically transformed HuT fibroblasts in human osteosarcoma HOS fibroblasts and modulation of actin expression upon elevation of tumorigenic potential. 385 66


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