Biomedical subjects

Y Yamamoto-Yamaguchi

Publications and source records attributed to Y Yamamoto-Yamaguchi.

At least 19 recordsLinked to original sources

PubMed1997

AML1a but not AML1b inhibits erythroid differentiation induced by sodium butyrate and enhances the megakaryocytic differentiation of K562 leukemia cells.

AML1 may play a role in growth and differentiation of cells along erythroid and/or megakaryocytic lineages, because a significant level of the AML1 gene is expressed in these cells. We overexpressed AML1a (without the transcription-activating domain) and AML1b (with the domain) proteins in K562 leukemia cells, which can be induced to differentiate into hemoglobin-producing cells and megakaryocytes. The AML1a-transfected K562 cells had a reduced capacity to differentiate in the presence of sodium n-butyrate but not in the presence of other inducers, such as hemin, 1-beta-D-arabinofuranosylcytosine, and herbimycin A. The AML1 antisense oligodeoxynucleotide but not the sense oligomer recovered its differentiation-inducing capacity in the presence of butyrate. On the other hand, AML1b conferred a similar differentiation-inducing capacity upon K562 cells transfected with vector alone. AML1a expression was associated with enhanced sensitivity to megakaryocytic differentiation induced by phorbol ester. These results provide evidence that AML1 proteins play a role in erythroid and megakaryocytic differentiation.

Antigens, CD↗

PubMed1997

Neplanocin A, a potent inhibitor of S-adenosylhomocysteine hydrolase, potentiates granulocytic differentiation of acute promyelocytic leukemia cells induced by all-trans retinoic acid.

Several neplanocin A analogs were synthesized and their growth-inhibiting and differentiation-inducing activities on myelogenous leukemia cells were examined. An adenosine kinase-ineffective analog of neplanocin A was effective in inducing differentiation, suggesting that phosphorylation of the nucleoside is not essential for inducing the differentiation of leukemia cells. Neplanocin A induced functional and morphological differentiation of HL-60 cells, but did not effectively induce differentiation of NB4, a cell line derived from a leukemia patient with t(15;17). However, these cells have been known to undergo granulocytic differentiation upon treatment with all-trans retinoic acid (ATRA), and are used as a model for differentiation therapy in acute promyelocytic leukemia. Preexposure of NB4 cells to low concentrations of neplanocin A greatly enhanced the ATRA-induced differentiation of the cells, whereas representative antileukemic drugs such as cytosine arabinoside and daunomycin did not enhance this differentiation. A clinical strategy that combines intermittent treatment with neplanocin A analogs and a low dose of ATRA may increase the clinical response and decrease the adverse effects of ATRA.

Adenosine↗

PubMed1996

Enhancement of activity of 1alpha, 25-dihydroxyvitamin D3 for growth inhibition and differentiation induction of human myelomonocytic leukemia cells by tretinoin tocoferil, an alpha-tocopherol ester of all-trans retinoic acid.

Tretinoin tocoferil is an alpha-tocopherol ester of all-trans retinoic acid (RA) and safely used in the treatment of skin ulcer. Tretinoin tocoferil inhibited proliferation of human promyelocytic leukemia HL-60 cells and induced granulocytic differentiation of the cells, but less than RA. alpha-Tocopherol did not affect differentiation of HL-60 cells, but at high concentrations enhanced its nitroblue tetrazolium (NBT)-reducing activity and expression of surface antigen CD11b, which are markers of myelomonocytic differentiation induced by RA. Tretinoin tocoferil increased NBT reduction in HL-60 cells treated with RA. It also enhanced the differentiation of HL-60 cells induced by dimethyl sulfoxide, phorbol-12-myristate 13-acetate or 1alpha,25-dihydroxyvitamin D3 (VD3). In combination with a low concentration of VD3, it induced the NBT-reducing activity of human monoblastic U937 cells very effectively. Moreover, it enhanced the differentiation of human myelomonocytic ML-1, THP-1, P39/TSU, and P31/FUJ cells induced by VD3. In combination with VD3, it synergistically inhibited the proliferation of HL-60, U937, ML-1, THP-1, P39/TSU, and P31/FUJ cells and decreased the effective concentration of VD3 to a 10(-10) mol/L level. Because tretinoin tocoferil was reported to induce neither retinoid-related toxicity nor teratogenicity, the therapeutic advantage of the use of it in treatment of myelomonocytic leukemia is suggested.

Antineoplastic Agents↗

PubMed1996

Enhancement of sensitivity of human lung adenocarcinoma cells to growth-inhibitory activity of interferon alpha by differentiation-inducing agents.

A low concentration of differentiation inducers such as dimethylsulphoxide (DMSO), sodium butyrate, hexamethylene bisacetamide and sodium phenylacetate greatly enhanced the antiproliferative effect in vitro and in vivo of interferon alpha (IFN-alpha) to several human lung adenocarcinoma cells. The agents induced morphological changes in the adenocarcinoma cells and the agents together with IFN-alpha-induced alkaline phosphatase activity, which is a typical marker of type II pneumocyte maturation. To understand the mechanism of the DMSO-enhanced interferon sensitivity, we examined the effect of DMSO on high-affinity IFN-alpha receptor and interferon-stimulated promoter-binding factors. The lung adenocarcinoma cells were not impaired in IFN-alpha receptor and interferon-stimulated gene transactivation factor 3 (ISGF-3). Our data suggest that the enhancement of interferon sensitivity in the lung adenocarcinoma cells acts downstream of the activation of ISGF-3.

Acetamides↗

PubMed1996

Reversible differentiation of human monoblastic leukemia U937 cells by ML-9, an inhibitor of myosin light chain kinase.

Human monoblastic leukemia U937 cells are induced to differentiate into monocytes and macrophages by various agents. We have shown that 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9), an inhibitor of myosin light chain kinase, induces differentiation of monocytoid leukemia cell lines U937 and THP-1 but not of myeloblastic leukemic ML-1 cell or erythroleukemia K562 cells. In the present study, we further analyzed the effect of ML-9 in comparison with that of 1 alpha, 25-dihydroxyvitamin D3 (VD3) a typical inducer of monocytic differentiation. ML-9 induced nitroblue tetrazolium (NBT)-reducing activity of U937 cell more rapidly than VD3: This differentiation marker was induced significantly after incubation with ML-9 and VD3 for 4 hours and 1 day, respectively. ML-9 also induced alpha-naphthyl acetate esterase (ANAE) activity, another monocytic differentiation marker, more rapidly than VD3. The maximum levels of these markers induced by ML-9 were comparable to those induced by VD3, but after removal of ML-9 from the medium by washing the cells, the expressions of theses markers decreased within 4 hours and reached basal levels in 1 day, indicating that ML-9's induction of expression of differentiation-associated phenotypes was reversible. The growth inhibition of U937 cells by ML-9 was also reversible. Similar effects were observed in another line of human monoblastic cells, THP-1. ML-9 had little or no effect on the morphology of U937 cells but increased the expression of monocyte-macrophage lineage-associated surface antigen, CD14, to some extent. Irreversible terminal differentiation induced by VD3 is associated with down regulation of the expression of c-myc and upregulation of the expression of c-fos and c-jun, but ML-9 did not affect the expression of these oncogenes appreciably. ML-9-induced differentiation was also reversible when the cells were cultured with cultured with ML-9 plus an anti-cancer drug such as 1-beta-D-arabino-furanosylcytosine or daunomycin. it became irreversible, however, upon simultaneous treatment with dexamethasone and transforming growth factor-beta 1 (TGF-beta 1), which did not induce differentiation of U937 cells but caused growth arrest of the cells in the G0/G1 phase of the cell cycle. These results suggest that ML-9 should be useful for studying the mechanisms of monocytic differentiation.

Antigens, Differentiation, Myelomonocytic↗

PubMed1996

Transforming growth factor beta and dexamethasone cooperatively enhance c-jun gene expression and inhibit the growth of human monocytoid leukemia cells.

Glucocorticoids inhibit the proliferation of lymphoid leukemia cells, whereas most myeloid leukemia cells are resistant to glucocorticoids. However, this study showed that glucocorticoids significantly and preferentially inhibited growth of monocytoid leukemia cells in combination with a low concentration of transforming growth factor beta (TGF beta). Combined 1 alpha,25-dihydroxyvitamin D3 and TGF beta markedly induced monocytic differentiation of U937 cells, whereas dexamethasone (Dex) and TGF beta essentially did not, although both combinations similarly inhibited the growth of U937 cells. The growth inhibition was accompanied by a block in the cell cycle progression from G1 to S phase (G1 arrest). Expression of glucocorticoid receptors was not affected by TGF beta, although they are induced during the monocytic differentiation of myelogenous leukemia cells and have increased sensitivity to glucocorticoids. The expression of TGF beta receptors also was not enhanced by Dex. TGF beta significantly stimulated glucocorticoid responsive element-mediated transcription activity. Combined Dex and TGF beta stimulated the expression of c-jun and c-fos early responsive genes in U937 cells, although Dex or TGF beta alone did not. The combination synergistically induced expression of c-jun gene, reaching a maximum level at 24 h. On the other hand, expression of c-fos gene was induced by TGF beta alone and increased additively in combination with Dex. Treatment with antisense oligonucleotide complementary to the first exon of c-jun mRNA reduced the growth-inhibitory effect of Dex and TGF beta in a dose-dependent manner. However, exposure of U937 cells to the sense oligomer of c-jun mRNA or an antisense oligomer of c-fos mRNA did not affect the growth inhibition. These results suggested that the preferential expression of c-jun and stimulation of glucocorticoid responsive element-mediated transactivation are closely associated with the growth arrest of U937 cells incubated with Dex and TGF beta.

Antineoplastic Agents, Hormonal↗

PubMed1995

19-Allylaminoherbimycin A, an analog of herbimycin A that is stable against treatment with thiol compounds or granulocyte-macrophage colony-stimulating factor in human leukemia cells.

Herbimycin A, a benzoquinonoid ansamycin antibiotic, reduces intracellular phosphorylation by some protein tyrosine kinases and inhibits the proliferation of malignant cells which express high tyrosine kinase activity. Herbimycin A inhibited the proliferation of human monoblastic leukemia U937 cells, but this inhibition was abrogated by the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF). On the other hand, a derivative of herbimycin A, 19-allylaminoherbimycin A, inhibited the proliferation of such cells without interference by the addition of GM-CSF. Phosphorylation of MAP kinase and c-myc expression induced by GM-CSF in U937 cells were inhibited by both herbimycin A and 19-allylaminoherbimycin A. The time courses of growth inhibition showed that the growth-inhibitory activity of herbimycin A in U937 cells was initially potent, but gradually decreased in the presence of GM-CSF. Thiol compounds, glutathione (GSH) and 2-mercaptoethanol, abrogated the inhibition of the growth of U937 cells by herbimycin A, but not by 19-allylaminoherbimycin A, like GM-CSF. Intracellular GSH content in U937 cells was increased by treatment with GM-CSF, and decreased with herbimycin A, but returned to the control level with the addition of GM-CSF to herbimycin A. In thin-layer chromatography, after in vitro incubation with herbimycin A and GSH, nothing could be detected at the position of intact herbimycin A, while 19-allylaminoherbimycin A was stably detected. These findings suggest that changes in the intracellular concentration of GSH play a role in the abrogation of the inhibition of U937 cell growth by herbimycin A. In the presence of GSH, 19-allylaminoherbimycin A inhibited the proliferation of U937 cells and Philadelphia chromosome-positive K562 cells more effectively than herbimycin A. Since GSH plays a role in detoxicating several anticancer drugs, 19-allylaminoherbimycin A may have therapeutic advantages over herbimycin A against some types of leukemia.

Antibiotics, Antineoplastic↗

PubMed1994

Three different cDNAs encoding mouse D-factor/LIF receptor.

Three cDNAs for mouse differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF) receptor were isolated from a cDNA library prepared from the liver of a pregnant mouse. A probe for screening was prepared by the RT-PCR method using human cDNA sequences as primers. The mouse D-factor receptor cDNA encoded 1,092 amino acids, which had a marked homology with the human counterpart and consisted of signal sequence, extracellular, transmembrane, and cytoplasmic domains. The WSXWS motif found in members of the cytokine receptor family was also present in the extracellular domain of the mouse D-factor receptor. A second form of cDNA that had a 501 bp insertion was isolated. The insertion introduced a stop codon so that the mRNA encoded the soluble receptor lacking transmembrane and intracellular domains. Because the insertion contained polyadenylation signals, two different sizes of mRNA encoding the soluble receptor were produced, depending on whether or not it utilized these signals. Transcripts utilizing these signals were 2.6-3 kb in size, and were very abundantly expressed in the liver. Transcripts that did not use these signals were longer than 5 kb and of similar size to the mRNA for the cellular receptor.

Amino Acid Sequence↗

PubMed1993

Pregnancy associated increase in mRNA for soluble D-factor/LIF receptor in mouse liver.

We examined the distribution of mRNAs for differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF) receptor in various mouse tissues by Northern blotting. A mouse cDNA fragment encoding the D-factor receptor was prepared by the RT-PCR method using human cDNA sequences as primers. The smallest mRNA (3 kb) was present in the liver, but not detectable in other tissues examined. Larger mRNAs (5 and 10 kb) were present in the placenta and the M1 cells, and also detectable in the liver, kidney, heart, lung, brain and embryos. Expression of 3 kb mRNA in the liver increased during pregnancy, being 20 times the initial level on day 15. D-factor receptor cDNAs were isolated from a cDNA library prepared from the liver of a pregnant mouse. Most of the cDNA clones encoded a soluble receptor. A cDNA probe specific for the cellular receptor did not hybridize with 3 kb mRNA in the liver. These results suggest that 3 kb mRNA encodes a soluble D-factor receptor and that the liver is the primary site of synthesis of this soluble receptor.

Amino Acid Sequence↗

PubMed1992

Prolongation by differentiation-stimulating factor/leukemia inhibitory factor of the survival time of mice implanted with mouse myeloid leukemia cells.

Mouse myeloid leukemic M1 cells can be induced to differentiate into macrophages by differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF). We examined the effect of D-factor on the survival times of syngeneic mice implanted with two different clones (T-22 and R-4) of M1 cells. D-factor induced differentiation and suppressed DNA synthesis of sensitive T-22 cells but not resistant R-4 cells in vitro. For in vivo experiments, we used recombinant mouse D-factor (rmD-factor) produced in mammalian cells, which is glycosylated and is more stable in vitro and in vivo than unglycosylated rmD-factor produced in Escherichia coli. Treatment with rmD-factor prolonged the survival times of mice implanted with T-22 cells but not R-4 cells.

Animals↗

PubMed1991

Both D factor/LIF and IL-6 inhibit the differentiation of mouse teratocarcinoma F9 cells.

Differentiation-stimulating factor (D factor)/leukemia inhibitory factor (LIF) and IL-6 are reported to be cytokines having multifaced functions including the induction of differentiation in mouse myeloid leukemia M1 cells. We here report that both D factor/LIF and IL-6 inhibit the differentiation of mouse teratocarcinoma F9 cells induced by retinoic acid alone or combined with dibutyryl cAMP. From the microscopic observation as well as Northern blot analysis using cDNA probes encoding several marker proteins for differentiation of F9 cells, we concluded that D factor/LIF and IL-6 are functionally closely related in the induction of differentiation in M1 cells and in the inhibition of F9 differentiation.

Alkaline Phosphatase↗

PubMed1990

Inhibition of development of Na(+)-dependent hexose transport in renal epithelial LLC-PK1 cells by differentiation-stimulating factor for myeloid leukemic cells/leukemia inhibitory factor.

Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor is a cytokine inducing differentiation of mouse myeloid leukemic M1-T22 cells. The effect of recombinant human D-factor on growth and differentiation of pig kidney LLC-PK1 cells was examined. LLC-PK1 cells did not concentrate alpha-methylglucoside during their early growth in culture but developed the capacity to concentrate this hexose as they reached confluence and their growth rate decreased. Purified D-factor caused dose-dependent inhibition of the development of this concentrative capacity. It did not affect the growth rate of the cells, but inhibited the formation of multicellular domes in confluent cultures. LLC-PK1 cells were found to have high-affinity binding sites (831 per cell) for D-factor with a dissociation constant of 197 pM.

Alkaline Phosphatase↗

PubMed1990

Protein factors that regulate the growth and differentiation of mouse myeloid leukaemia cells.

We have purified and characterized several protein factors that regulate the growth and differentiation of mouse myeloid leukaemia M1 cells. The differentiation factor (D-factor) from conditioned medium (CM) of Ehrlich ascites tumour cells is a glycoprotein of Mr 40,000-50,000. Its amino acid sequence was found to be almost identical to that of leukaemia inhibitory factor (LIF) from Krebs II ascites cells. The differentiation inhibitory factor (I-factor) from the CM of variant M1 cell clones which were resistant to several differentiation inducers is a basic protein of apparent Mr 68,000. The growth inhibitory factor (GI-factor) that specifically inhibits the partially differentiated and still growing monocytic leukaemia M1 cells was isolated from the CM of a clone of M1 cells resistant to the differentiation inducers. This GI-factor is a basic protein with an Mr of 25,000. Regulation by these protein factors together with other known cytokines of growth and differentiation of M1 cells is reported.

Animals↗

PubMed1989

Contrasting effect of IFN-gamma and IFN-alpha/beta on differentiation of some clones of mouse myeloid leukemic cells.

Mouse myeloid leukemic M1 cells are induced to differentiate into macrophage-like cells by a differentiation-inducing factor (D-factor) and various agents. IFN-gamma alone did not induce differentiation of clone T22-3 of M1 cells but inhibited their differentiation by D-factor. That is, IFN-gamma at 4 U/ml inhibited 50% of phagocytic activity of T22-3 cells induced by 7 x 10(-11) M D-factor. In addition, it inhibited the induction of lysozyme activity and morphological differentiation of these cells by D-factor. IFN-gamma also inhibited dexamethasone-induced differentiation of T22-3 cells. Previously interferon-alpha/beta was shown not to induce differentiation of M1 cells itself, but to enhance induction of their differentiation by D-factor. The present study showed that IFN-alpha/beta and IFN-gamma had opposite effects on induction of differentiation of T22-3 cells by D-factor. The effect of IFN-gamma on the differentiation of M1 cells varied with the clone of M1 cells used: IFN-gamma inhibited D-factor-induced differentiation of cells of clones T22-3 and S2, but induced differentiation of cells of clones B24 and S1.

Animals↗

PubMed1989

Genomic cloning and heterologous expression of human differentiation-stimulating factor.

Differentiation-stimulating factor (D-factor) purified from mouse Ehrlich ascites cells was sequenced partially and found to be almost identical to leukemia inhibitory factor (LIF) from mouse Krebs II ascites cells. In comparison to LIF, D-factor had an additional amino-terminal serine residue. Using synthetic oligonucleotide probes designed from the murine D-factor sequence, we cloned the human gene encoding D-factor. A partial D-factor cDNA was cloned from COS-1 cells transfected with the human D-factor gene under the control of a heterologous promoter. We used this cDNA to construct a vector for direct expression of the protein in Escherichia coli. A mammalian cell expression vector was constructed using the signal sequence of interferon-alpha A linked to the D-factor cDNA. Both forms of recombinant human D-factor were active on the murine myeloid leukemia cell line M1 in a dose- and time-dependent manner for the inhibition of [3H]thymidine incorporation, and also induced phagocytosis, Fc receptor expression, and prostaglandin E2 synthesis by M1 cells.

Amino Acid Sequence↗

PubMed1989

Combined effects of differentiation-inducing factor and other cytokines on induction of differentiation of mouse myeloid leukemic cells.

Mouse myeloid leukemic M1 cells are induced to differentiate into macrophage-like cells by differentiation-inducing factors (D-factors) and granulocyte colony-stimulating factor. We examined the effects of recombinant human tumor necrosis factor (rTNF), lymphotoxin (rLT) and interleukin 1 (rIL-1) on the induction of differentiation of M1 cells, compared with the effects of D-factor purified from the conditioned medium of mouse Ehrlich ascites tumor cells and recombinant human granulocyte colony-stimulating factor (rG-CSF). rIL-1 induced phagocytic activity, a typical marker of cell differentiation, in at most 30% of M1 cells at concentrations ranging from 10(-10) M to 10(-7) M. The differentiation-inducing activity of rIL-1 was similar to that of rG-CSF and less than that of D-factor. rTNF induced phagocytic activity in 14% of M1 cells only at a high concentration (10(-7) M). rLT did not induce differentiation of the cells even at 10(-7) M. rTNF stimulated induction of differentiation of M1 cells by D-factor, rG-CSF or rIL-1 by two or three fold. The combination of any two of the cytokines D-factor, rG-CSF and rIL-1 induced differentiation of M1 cells more efficiently than any of these cytokines alone. Moreover, the combination of three cytokines rG-CSF, rIL-1 and rTNF, all of which are known to be produced by macrophages, was more effective than the combination of any two of these cytokines in induction of differentiation of M1 cells.

Animals↗

PubMed1986

Induction by recombinant human granulocyte colony-stimulating factor of differentiation of mouse myeloid leukemic M1 cells.

The effect of recombinant human granulocyte colony-stimulating factor (G-CSF) on induction of differentiation of mouse myeloid leukemic M1 cells was examined. Purified G-CSF caused dose-dependent induction of phagocytic activity and lysozyme activity in M1 cells. Its half-maximally effective concentration was 10 ng/ml. On treatment of M1 cells with G-CSF (100 ng/ml) for 4 days, 30-50% of the cells differentiated morphologically into macrophage cells; 30-40% of the cells were blast cells and 20-30% of the cells were forms intermediate between blastic cells and mature macrophages.

Animals↗

PubMed1986

Specific binding of a factor inducing differentiation to mouse myeloid leukemic M1 cells.

A factor inducing differentiation of mouse myeloid leukemic M1 cells into macrophages (differentiation-inducing factor, D-factor), which was purified to homogeneity from conditioned medium of mouse Ehrlich ascites tumor cells, could be iodinated without detectable loss of biological activity. The binding of 125I-D-factor to M1 cells was specific; the binding was inhibited competitively by D-factor derived from Ehrlich cells and mouse fibroblast L929 cells, but not by other growth factors or D-factor derived from differentiated M1 cells. The latter differs from D-factor of Ehrlich cells and L929 cells in antigenicity and molecular weight. At 21 degrees C, the binding was saturated at 370 pM 125I-D-factor. M1 cells showed a high affinity for 125I-D-factor (dissociation constant, 1.0 X 10(-10) M) and expressed a small number of binding sites (170 per cell). Specific binding of 125I-D-factor was observed only to several clones derived from M1 cells, including those sensitive and resistant to induction of differentiation by D-factor.

Animals↗