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)

Human T-cell-leukemia-virus-type-1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The T-cell-targeting immunosuppressants, FK506 and cyclosporin A (CsA), suppressed proliferation of the HAM/TSP-derived T-cell lines, H89-59, H89-79 and H109. FK506 and CsA also reduced expression of the proto-oncogenes, c-myc and c-fos, but not c-jun and interleukin-2-receptor-alpha (IL-2R alpha) gene in H109 cells. The growth-inhibitory effects of FK506 and CsA were not abrogated by interleukin 2 (IL-2). These results suggest that the inhibitory effects of FK506 and CsA are independent of IL-2, and are associated with the reduction of c-myc and c-fos gene expression.
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PMID:FK506 and cyclosporin a regulate proliferation and proto-oncogene expression in HTLV-1-associated myelopathy/tropical-spastic-paraparesis-derived T cells. 768 33

To analyze the effect of human T-cell leukemia virus type I (HTLV-I) on cellular gene expression and its relation to tumorigenesis, two lines of transgenic mice carrying the long terminal repeat (LTR)-env-pX-LTR regions of the HTLV-I genome were produced. The transgene was expressed in many organs, including the brain, salivary gland, spleen, thymus, skin, muscle, and mammary gland. We found that the expression of the c-fos and c-jun genes, but not of the lyn and c-myc genes, was augmented 2- to 20-fold in histologically normal skin and muscle of these mice. The augmentation was tissue specific, suggesting the involvement of a cellular factor in the transgene action. In these mice, a three to seven times higher incidence of tumors was seen as compared with the control mice. These tumors included mesenchymal tumors, such as fibrosarcoma, neurofibroma, and lipoma, and adenocarcinomas of the mammary gland, salivary gland, and lung. The c-fos and c-jun genes were also activated in these tumors. The possible roles of elevated c-fos and c-jun gene expression in tumorigensis are discussed.
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PMID:Augmentation of c-fos and c-jun expression in transgenic mice carrying the human T-cell leukemia virus type-I tax gene. 773 61

Overexpression of c-myc, c-myb and c-fos proto-oncogene has been observed in many leukemia cells. However, a relation between those oncogene expressions and prognosis of the leukemia is not known in Indonesia. In order to elucidate the relation, expression of those oncogenes in leukemia cells from 52 patients in Indonesia was examined by Northern blot analysis and was compared with prognosis of the disease. The leukemia patients who survived for more than 2 years were 37% of the 52 patients. Many of the samples expressed c-myc mRNA (92%). Although strong expression of c-myb and c-fos mRNA was detected in the samples (c-myb expression in 35% of the leukemia cells and c-fos in 52%), those co-expressions with c-myc mRNA did not alter the prognosis. On the contrary, all of the 4 patients suffering from leukemia which did not express c-myc mRNA survived for more than 2 years. Therefore, c-myc expression in leukemia cells may be used as an indicator for deciding prognosis of the leukemia patients in Indonesia.
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PMID:A relation between c-myc expression and prognosis of leukemia patients in Indonesia. 773 3

Etoposide (VP-16) is one of several DNA-damaging agents that induce subcellular structural changes associated with apoptosis. VP-16 exerts its DNA-damaging and cytotoxic effects subsequent to interference with DNA topoisomerase II activity. VP-16 also stimulates c-jun and c-fos mRNA expression in some cell lines, including human leukemia K562 and HL-60 cells. To compare the temporal relationship between drug-induced c-jun expression and apoptosis, we examined cell morphology, cell viability, DNA integrity, and c-jun induction during VP-16 treatment of K562 and HL-60 cells. VP-16 (10 microM)-induced internucleosomal DNA damage and nuclear fragmentation were readily apparent within 6 hr in HL-60 cells but were absent in K562 cells treated for up to 24 hr. Some internucleosomal DNA damage was observed in K562 cells but only after treatment with 100 microM VP-16 for 24 hr. In contrast, VP-16-induced DNA single-strand breaks, VP-16-induced topoisomerase II/DNA covalent complex formation, and VP-16-mediated growth inhibition were similar in K562 and HL-60 cells. Also, the time course of VP-16-induced c-jun mRNA expression was comparable for both K562 and HL-60 cell lines. Western blot analysis of whole-cell lysates showed that Bcl-2 protein levels were 13-fold greater in HL-60 cells than in K562 cells. Thus, the resistance of VP-16-treated K562 cells to apoptosis was not attributable to protection by Bcl-2. Furthermore, the relatively high levels of Bcl-2 in HL-60 cells were not sufficient to protect these cells against apoptosis. Together, our results indicate that the temporal coupling of VP-16-induced DNA damage, c-jun expression, and apoptosis is cell type specific and suggest that different signaling pathways for apoptosis are operating in these two human leukemia cell lines.
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PMID:Differential induction of etoposide-mediated apoptosis in human leukemia HL-60 and K562 cells. 796 39

We investigated the expression of c-fos gene product in peripheral blood mononuclear cells of patients with smouldering adult T-cell leukaemia (ATL) and healthy human T-lymphotropic virus type-I (HTLV-I) carriers by an immunofluorescence assay, using a mouse monoclonal antibody (FO-120) specific for fos gene product. Peripheral blood mononuclear cells derived from healthy HTLV-I carriers were rarely positive for FO-120, less than 2% of the cells weakly reacted with FO-120, whereas positive cells were detected in more than about 10% of cells from patients with smouldering ATL. FO-120 appears to be a useful tool for detecting smouldering ATL in asymptomatic HTLV-I infected people without using molecular techniques.
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PMID:Expression of fos proto-oncogene product by monoclonal antibody FO-120 in smouldering adult T-cell leukaemia (ATL). 801 29

Interleukin-4 inhibits several monocyte functions like A23187-induced expression of cytokines and c-fos and c-jun proto-oncogene mRNA expression. In an attempt to elucidate the mechanism by which this inhibitive effect is mediated, we compared the effect of IL-4 on A23187-induced c-fos and c-jun mRNA expression in conjunction with inhibitors that selectively inhibit the cyclooxygenase dependent (indomethacin) and lipoxygenase dependent (NDGA) pathway of arachidonic acid (AA) metabolism. NDGA inhibited A23187-induced c-fos mRNA expression by a similar magnitude as IL-4, whereas the effect of indomethacin was only minor. A23187-induced c-jun mRNA expression was not affected by indomethacin and only slightly inhibited by NDGA. These results indicate that in human monocytes c-fos mRNA expression is at least partly controlled by the lipoxygenase directed pathway of AA metabolism, whereas the cyclooxygenase dependent pathway is not involved in the regulation of proto-oncogene expression. This was supported by the finding that leukotriene B4 (LTB4) and 5'-hydroperoxyeicosatetraenoic acid (5'-HPTETE), which are two lipoxygenase metabolites, strongly induced c-fos mRNA, whereas c-jun mRNA expression was slightly affected. However, the inhibitive effect of IL-4 could not be ascribed to a reduced production of LTB4 suggesting that the mode of IL-4 action lies behind the conversion of AA to 5'-HPETE and LTB4.
Leukemia 1994 Jul
PMID:Interleukin-4-mediated inhibition of C-Fos mRNA expression: role of the lipoxygenase directed pathway. 803 10

In this report we identify the specific isozymes of protein kinase C (PKC) that are involved in c-fos and c-jun mRNA accumulation in the rat basophilic leukemia cell line RBL-2H3. These cells could be largely depleted of the endogenous PKC isozymes by chronic treatment with phorbol 12-myristate 13-acetate followed by permeabilization of the cells with streptolysin O. The reconstitution of these cells with defined concentrations of either PKC-beta or PKC-epsilon up to 10 nM and 20 nM, respectively, induced c-fos and c-jun in a dose-dependent manner. At high concentrations of PKC-beta and -epsilon the induction of c-fos and c-jun was independent of the aggregation of the high-affinity IgE receptors (Fc epsilon type I receptors). In contrast, at limiting concentrations of these two PKC isozymes, 1 nM, the increase in c-fos and c-jun mRNAs was dependent on the aggregation of the Fc epsilon type I receptors. Unlike PKC-beta and -epsilon, PKC-alpha and PKC-delta failed to reconstitute c-fos and c-jun induction at any dose over the range examined. We conclude that PKC-beta and PKC-epsilon serve as a link between the cell surface receptor and gene expression.
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PMID:Protein kinases C-beta and C-epsilon link the mast cell high-affinity receptor for IgE to the expression of c-fos and c-jun. 805 50

Optimal gene replacement protocols would include both inhibition of the endogenous gene and overexpression of the preferred (or mutant) gene. We have developed a novel gene transfer method to test whether antisense-resistant genes (designed by deletion of antisense RNA target sequences) can replace the function of endogenous genes. Immunoprecipitation studies demonstrated that inducible anti-fos RNA (antisense directed against the c-fos gene) reduces endogenous c-fos expression by 90%, but did not affect the transfected antisense-resistant mutant c-fos genes. Cell growth studies demonstrated that full-length and minimally truncated c-fos expression vectors could restore serum-induced DNA synthesis but that C-terminally truncated Fos mutants including FBR v-fos could not. Transcriptional studies demonstrate that the endogenous c-fos protein contributes to AP-1 activity and normally suppresses regulated SRE (serum response element) activity. This "gene transplant" method for inhibition of endogenous genes and replacement with preferred genes has implications for gene therapy of hereditary hematologic disorders and for the correction or "repair" of oncogenes or tumor suppressor genes in leukemias and lymphomas.
Leukemia 1994 Apr
PMID:Gene transplantation: combined antisense inhibition and gene replacement strategies. 815 83

The human osteosarcoma cell culture HOS does not produce matrix metalloproteinases (MPs). However, after transformation with the Ki-ras oncogene, the resulting culture (KHOS) produced readily detectable MPs. The molecular weight of the major MP was 66 kDa, while the molecular weights of two other minor bands were 71 kDa and 60 kDa. The activity of all three enzymes was inactivated by treatment with ethylene diaminetetra acetic acid, indicating that they are probably MPs. The substrate preference of the 66-kDa MP (in decreasing order) was gelatin and collagens V, I, III, and IV. Treatment of the MPs with p-aminophenylmercuric acetate led to the appearance of 62-kDa activated enzyme. The MP produced by KHOS cells did not react with the monoclonal anti-rat stromelysin antibody MC. Treatment of KHOS cells with retinoic acid and dexamethasone, which are known to suppress c-fos/c-jun and AP-1, suppressed the production of the MPs. Therefore, the activation of MPs by Ki-ras in KHOS cells may involve c-fos/c-jun and the AP-1-responsive pathway.
Leukemia 1994 Apr
PMID:Activated production of metalloproteinases in Ki-ras-transformed human osteosarcoma cells. 815 1

Human T-cell leukemia virus type I causes adult T-cell leukemia and tropical spastic paraparesis, and its regulator protein Tax has been implicated in the pathogenic activity of human T-cell leukemia virus type I. Tax activates transcription of viral and cellular genes through specific enhancers: the 21-bp enhancer of human T-cell leukemia virus type I, the nuclear factor kappa B (NF-kappa B)-binding site of the interleukin 2 receptor alpha gene, and the serum-responsive element of c-fos. Tax binds to enhancer-binding proteins including cAMP-responsive element-binding protein, cAMP-responsive element modulator, transcription factor NF-kappa B p50 and p67SRF, and associates with each enhancer DNA indirectly. In addition to this mechanism, we report here that Tax binds to inhibitory factor kappa B gamma (I-kappa B) gamma, which forms a complex with NF-kappa B protein heterodimer p50-p65 or homodimer p50-p50 and retains them in the cytoplasm. Tax binding to I-kappa B gamma induces nuclear translocation of NF-kappa B p65. In association with this nuclear translocation of p65, transcription directed by the kappa B enhancer is strongly activated. Tax binds to the ankyrin motifs of I-kappa B gamma, suggesting its possible interaction with many other proteins carrying ankyrin motifs contributing to various regulatory processes. This is a different mechanism of transcriptional activation by the oncoprotein Tax and seems to be independent from the trans-activation through indirect binding to enhancer DNAs.
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PMID:Tax protein of human T-cell leukemia virus type I binds to the ankyrin motifs of inhibitory factor kappa B and induces nuclear translocation of transcription factor NF-kappa B proteins for transcriptional activation. 817 Sep 51


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