Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the expression of the protooncogenes of the myc and ras family in HT29 cells and in three differentiated clonal cell lines derived from this colon carcinoma cell line. In contrast to the decrease in myc expression seen when leukemia cells are induced to differentiate, we have found no changes in expression of the myc gene family in differentiated colon carcinoma cells. However, a greater than 5-fold increase in expression of sequences which hybridize to Ha-ras was observed in cells which secrete mucin, with a smaller increase seen in expression of Ki-ras in the same cells. This increase was not seen in cells which exhibit vectorial transport of water and ions, and which are not mucus-secreting. All differentiated lines were less tumorigenic in nude mice than the parental HT29 cells, irrespective of the level of ras expression. These results are consistent with the reports that ras expression is highest in the most differentiated cells of the colon and is substantially decreased in metastatic human colon tumors as compared to primary colon tumors. The data also suggest that a high level of ras gene expression is a marker for a particular differentiated state in colon cells rather than being directly equated with transformation or tumorigenicity. Hence, the results may reflect on some of the discrepancies concerning ras gene expression in human colon and other tumors which appear in the literature.
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PMID:Overexpression of ras in mucus-secreting human colon carcinoma cells of low tumorigenicity. 359 36

We have studied by means of DNA-mediated gene transfer the activation of protooncogenes in human myeloid leukemias that represent various stages of myeloid differentiation. DNA from three cell lines, HL-60 (promyelocytic leukemia), Rc2a (myelomonocytic leukemia), and KG-1 (acute myeloblastic leukemia), was capable of transforming NIH/3T3 cells. Hybridization analysis indicated that, in all three tumor cell lines, the N-ras oncogene was activated. The cell lines U-937 ("histiocytic lymphoma") and K-562 (erythroblastic leukemia) yielded no transforming DNA. Fresh leukemia cells derived from an acute myelomonocytic leukemia patient and from a juvenile chronic myelogenous leukemia patient contained an activated N-ras and c-Ki-ras oncogene, respectively. DNA from some other myelogenous leukemia patients was not able to transform NIH/3T3 cells. Our results indicate that hematopoietic tumors of the myeloid lineage may contain oncogenes active in NIH/3T3 cell transformation and that, in particular, the N-ras oncogene may be activated in tumors representing various stages of maturation.
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PMID:Oncogene activation in human myeloid leukemia. 385 67

Among 16 leukemia patients with abnormalities of the short arm of chromosome 12 (12p) were found 5 patients with an increased number of marrow basophils and a special M2 cytological feature. This new correlation between 12p abnormalities and M2-baso phenotype is presented. The localisation of c-k ras 2 genes at the same 12p site suggests a possible mutation of this c-oncogene.
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PMID:[Acute myeloblastic leukemia with involvement of the basophilic cell line and anomalies of the short arm of chromosome 12 (12p)]. 392 6

Recent studies have demonstrated that the cellular tumour antigen p53 (ref. 1) can complement activated ras genes in the transformation of rat fibroblasts, suggesting that the gene encoding p53 may act as an oncogene. Here, by using in situ chromosomal hybridization, we have mapped the p53 gene to human chromosome 17, at bands 17q21-q22, the region containing one of the breakpoints in the translocation t(15;17) (q22;q21) associated with acute promyelocytic leukaemia (APL). Hybridization of p53 and erb-A (17q11-q12) probes to malignant cells from three APL patients indicated that the p53 gene is translocated to chromosome 15 (15q+), whereas erb-A remains on chromosome 17. Analysis of variant translocations demonstrates that the 15q+ chromosome contains the conserved junction, suggesting a role for p53 in the pathogenesis of APL. However, rearrangements of the p53 gene were not detected on Southern blotting of DNA from leukaemic cells of four APL patients with t(15;17).
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PMID:Translocation of the p53 gene in t(15;17) in acute promyelocytic leukaemia. 392 42

There is now good evidence that the cellular protein, p53, is involved in the transformation process, although its precise role is unknown. It was reported recently that expression of the p53 gene can immortalize cells and that the p53 gene can replace the myc oncogene in a myc-ras immortalization/transformation assay. We have investigated whether p53 is involved in the progression towards the neoplastic state in vivo and report here that erythroleukaemic cell lines transformed by different isolates of Friend leukaemia virus show altered expression of the cellular p53 gene. High levels of p53 protein are found in certain lines, but the protein is undetectable in others. This heterogeneity in p53 gene expression is associated with heterogeneity in tumorigenicity. We demonstrate that genomic rearrangements are responsible for p53 gene inactivation in these cell lines and that they occur in vivo during the natural progression of Friend virus-induced erythroleukaemia.
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PMID:Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus. 399 Jul 96

A new acute transforming type C retrovirus was isolated from mice inoculated with a virus stock obtained by iododeoxyuridine induction of methylcholanthrene-transformed C3H/10T1/2 mouse cells. This virus, designated 3611-MSV, transforms embryo fibroblasts and epithelial cells in culture and induces fibrosarcomas in vivo. 3611-MSV is replication defective, requiring a type C helper virus for propagation both in vitro and in vivo. By using endpoint transmission of 3611-MSV to MMCE C17 mouse and FRE 3A rat cells, several nonproductively transformed clonal cell lines have been derived. Pseudotype virus stocks obtained from such clones transform cells in vitro, are highly oncogenic in vivo, and exhibit host range and serological properties that are characteristic of their helper virus component. Analysis of viral antigen expression in 3611-MSV-transformed cells has led to the demonstration of a 90,000-molecular-weight (Mr) polyprotein and a 75,000-Mr probable cleavage product, both containing the amino-terminal murine leukemia virus gag gene proteins p15 and p12. In contrast to gene products of many previously described mammalian transforming viruses, 3611-MSV-encoded polyproteins lack detectable protein kinase activity, and 3611-MSV-transformed cells resemble chemically transformed cell line C3H/MCA-5, from which 3611-MuLV was originally derived, in that they do not exhibit elevated levels of phosphotyrosine. By using molecular hybridization the 3611-MSV transforming gene was found to be distinct from previously described mammalian cellular oncogenic sequences, including c-ras, c-abl, c-fes, c-fms, c-sis, and c-mos.
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PMID:New mammalian transforming retrovirus: demonstration of a polyprotein gene product. 630 Apr 62

A molecular clone containing part of the transforming gene from two human sarcoma cell lines, HT1080 and RD, has been obtained and shown to represent a new member of the human ras gene family. The transforming gene has undergone no major rearrangements and has not been amplified in either sarcoma cell line. The major transcript from the gene is 2,200 nucleotides long and is present at the same levels in both normal fibroblasts and tumour cells. The same gene is also activated in HL60, a promyelocytic leukaemia line and in SK-N-SH, a neuroblastoma line. The gene, N-ras, is located on chromosome 1.
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PMID:Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1. 630 21

The mechanism of leukaemogenic transformation by human T-cell leukaemia/lymphoma virus (HTLV), a retrovirus implicated in the aetiology of certain adult T-cell leukaemias and lymphomas, is unknown but is conceivably associated with the expression of the cellular analogues of retroviral oncogenes. The HUT-102 cell line, derived from a cutaneous T-cell lymphoma and infected with HTLV, expresses several cellular oncogenes. It is unusual among haemopoietic cell lines in that one of these is c-sis, the gene from which the oncogene v-sis of the simian sarcoma virus was derived, and perhaps the gene for platelet-derived growth factor (PDGF). To explore the possible role of c-sis expression in HTLV-induced disease, we have obtained cDNA clones of c-sis from HUT-102 cells. Here we describe two such clones and report that one of them transforms NIH-3T3 cells. This is the first example of transformation of NIH-3T3 cells by a human onc gene other than c-ras or Blym, as well as the first demonstration of transformation by a human cDNA clone.
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PMID:Transformation of NIH 3T3 cells by a human c-sis cDNA clone. 632 94

Five unrelated mouse tumours have been shown to carry activated transforming genes using the NIH/3T3 transfection assay. Three of these tumours, a T-cell lymphoma, a fibrosarcoma and a macrophage tumour, were found to carry an activated c-Ki-ras gene. A c-Ha-ras gene was shown to be activated in a myeloid leukaemia and a recently identified member of the 'ras' gene family, N-ras, was found to be activated in a lung carcinoma. The T-cell lymphoma, L5178Y-ES, is a more aggressively growing metastatic variant which arose spontaneously from the parental tumour, L5178Y-E. Although DNA from both parental and variant tumours was shown to transfer a genetic marker to recipient cells equally well, only the metastatic variant carried an activated c-Ki-ras gene detectable by transfection. The altered growth behaviour of the L5178Y-ES cells may therefore be the result of the spontaneous activation of the c-Ki-ras gene after the lymphoma cells had already become tumorigenic.
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PMID:Three different activated ras genes in mouse tumours; evidence for oncogene activation during progression of a mouse lymphoma. 632 95

Human tumour cell lines of various histological origin contain genes that can transform NIH 3T3 cells in culture. Most frequently the gene is an activated K-ras gene, more rarely an activated H-ras gene, and sometimes the recently discovered N-ras. Other transforming genes, distinct from ras, have been found in B- and T-cell leukaemias. Since most of the transforming genes have been identified in cell lines, it is still unclear at what stage the genes become activated. We have therefore initiated a study to determine if the presence of a transforming gene correlates with the clinical course of a malignant disease. Here we demonstrate the presence of a transforming N-ras gene in bone marrow cells from a patient with acute myeloblastic leukaemia at the outbreak of the acute disease phase. Fibroblast DNA from the same patient was not transforming. In contrast to HL-60 cells, no alteration of the myc gene was detected.
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PMID:Activation of N-ras gene in bone marrow cells from a patient with acute myeloblastic leukaemia. 658 53


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