Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The exposure of human lymphoid leukemia Molt 4B cells to sodium 1-monolinolenin (SML) which was isolated from the leaves of Italian ryegrass (Lolium multiflorum Lam) and identified by Mass, and (1)H- and (13)C-NMR, led to both growth inhibition and induction of programmed cell death (apoptosis). Morphological change showing apoptotic bodies was observed in the Molt 4B cells treated with SML. The fragmentation by SML of DNA to oligonucleosomal-sized fragments, that is a characteristic of apoptosis, was observed to be both concentration- and time-dependent. These findings suggest that growth inhibition by SML of Molt 4B cells results from the induction of apoptosis in the cells.
Int J Mol Med 2001 Mar
PMID:Sodium 1-monolinolenin isolated from Italian ryegrass (Lolium multiflorum Lam) induces apoptosis in human lymphoid leukemia Molt 4B cells. 1117 5

The Bcr/Abl P190 oncoprotein is responsible for the development of Philadelphia-chromosome positive acute lymphoblastic leukemia (ALL). The Bcr moiety in Bcr/Abl activates the Abl tyrosine kinase, an ingredient essential for the transforming capability of Bcr/Abl. Residues 1-63 of Bcr form an N-terminal oligomerization domain and are key to Abl activation in vitro. Mice transgenic for P190 BCR/ABL reproducibly develop an aggressive B-lineage lymphoblastic leukemia/lymphoma. Here we test the hypothesis that residues 1-63 of Bcr have a major in vivo contribution to the oncogenicity of Bcr/Abl P190 by the generation of mice transgenic for an N-terminal deleted form of P190. We find that although the transgene is expressed in the bone marrow of mice at an early age, the incidence of leukemogenesis is greatly diminished as compared to mice transgenic for non-mutated P190 Bcr/Abl. Sporadic hematological malignancies which did develop showed decreased levels of phosphotyrosine as compared to those of wild-type P190 transgenics, although Ras was activated. These results demonstrate that the Bcr oligomerization domain contributes to the oncogenicity of Bcr/Abl in vivo.
Int J Mol Med 2001 Apr
PMID:The Bcr N-terminal oligomerization domain contributes to the full oncogenicity of P190 Bcr/Abl in transgenic mice. 1125 72

The exposure of human lymphoid leukemia Molt 4B cells to sesamolin, a component of sesame seed led to both growth inhibition and the induction of apoptosis. Morphological change showing apoptotic bodies was observed in the cells treated with sesamolin. The fragmentation of DNA by sesamolin to oligonucleosomal-sized fragments that are characteristics of apoptosis was observed to be concentration- and time-dependent. These findings suggest that growth inhibition of Molt 4B cells by sesamolin results from the induction of apoptosis in the cells.
Int J Mol Med 2001 Apr
PMID:Sesamolin from sesame seed inhibits proliferation by inducing apoptosis in human lymphoid leukemia Molt 4B cells. 1125 75

The exposure of human lymphoid leukemia Molt 4B cells to sesaminol, a component of sesame oil led to both growth inhibition and the induction of apoptosis. Morphological change showing apoptotic bodies was observed in the cells treated with sesaminol. The fragmentation of DNA by sesaminol to oligonucleosomal-sized fragments that are characteristics of apoptosis was observed to be concentration- and time-dependent. These findings suggest that growth inhibition of Molt 4B cells by sesaminol results from the induction of apoptosis in the cells.
Int J Mol Med 2001 May
PMID:Sesaminol from sesame seed induces apoptosis in human lymphoid leukemia Molt 4B cells. 1129 8

The role of inflammation in the early genesis of certain malignancies has recently been appreciated. Interleukin (IL)-15, a proinflammatory cytokine and growth factor, is required for lymphocyte homeostasis. Intriguingly, the expression of IL-15 protein is tightly controlled by multiple posttranscriptional mechanisms, suggesting that inappropriate expression of IL-15 may be detrimental to the host. We recently engineered a transgenic mouse in which the normal posttranscriptional control of IL-15 is eliminated, thereby overexpressing the murine IL-15 protein. IL-15 transgenic mice have early expansions in NK and CD8+ T lymphocytes and later develop fatal lymphocytic leukemia with a T-NK phenotype. This article recapitulates the phenotype of these IL-15 transgenic mice and discusses the utility of this model as a tool to further our understanding of leukemogenesis.
Blood Cells Mol Dis
PMID:Fatal leukemia in interleukin-15 transgenic mice. 1135 83

N-cadherin, a cell adhesion molecule normally found in neural cell tissue, has been found recently to be expressed on the surface of malignant T-cells. The function of N-cadherin on these cells remains unclear. Heterotypic assays between Molt-3 T lymphoblastic leukemia cells and Caco-2 epithelial monolayers were examined under different conditions to assess the functional role of N-cadherin. The results indicate that adherence of Molt-3 cells to Caco-2 monolayers was reduced significantly following pretreatment of Molt-3 cells with 100 microM of an N-cadherin-derived antagonist decapeptide. In contrast, pretreatment of Molt-3 cells with an anti-N-cadherin antibody raised against the first 20 amino acids of N-cadherin sequence led to a surprisingly marked enhancement of Molt-3 cell adherence to Caco-2 monolayers. In addition, the presence of anti-N-cadherin antibody neutralized the inhibitory effect of anti-ICAM-1 on Molt-3 adhesion to Caco-2 monolayers. This novel finding demonstrates that external stimulus through the N-cadherin amino terminus can modulate adhesion of malignant T-cells to epithelia and may promote their ability to invade or metastasize to inflammatory sites.
Mol Cell Biochem 2002 Apr
PMID:N-cadherin involvement in the heterotypic adherence of malignant T-cells to epithelia. 1208 63

The exposure of human lymphoid leukemia Molt 4B cells to diol- and triol-types of phytol which were synthesized and identified by Mass, and 1H- and 13C-NMR, led to both growth inhibition and induction of programmed cell death (apoptosis). Morphological changes showing apoptotic bodies were observed in the Molt 4B cells treated with diol- and triol-types of phytol. The fragmentations of DNA by the diol- and triol-types of phytol to oligonucleosomal-sized fragments, that is a characteristic of apoptosis, were observed to be both concentration- and time-dependent. These findings suggest that growth inhibition of Molt 4B cells by the diol- and triol-types of phytol results from the induction of apoptosis in the leukemic cells.
Int J Mol Med 2002 Nov
PMID:Diol- and triol-types of phytol induce apoptosis in lymphoid leukemia Molt 4B cells. 1237 91

Oncoprotein E2a/Pbx1 is produced by the t(1;19) chromosomal translocation of human pre-B acute lymphoblastic leukemia. E2a/Pbx1 blocks differentiation of primary myeloid progenitors but, paradoxically, induces apoptosis in established pre-B-cell lines, and no transforming function of E2a/Pbx1 has been reported in cultured lymphoid progenitors. Here, we demonstrate that E2a/Pbx1 induces immortal proliferation of stem cell factor (SCF)-dependent pro-T thymocytes by a mechanism dependent upon both its transactivation and DNA-binding functions. E2a-Pbx1 cooperated with cytokines or activated signaling oncoproteins to induce cell division, as inactivation of conditional E2a/Pbx1 in either factor-dependent pro-T cells or pro-T cells made factor independent by expression of Bcr/Abl resulted in pro-T-cell quiescence, while reactivation of E2a/Pbx1 restored cell division. Infusion of E2a/Pbx1 pro-T cells in mice caused T lymphoblastic leukemia and, unexpectedly, acute myeloid leukemia. The acute lymphoblastic leukemia did not evidence further maturation, suggesting that E2a/Pbx1 establishes an early block in pro-T-cell development that cannot be overcome by marrow or thymic microenvironments. In an E2a/Pbx1 pro-T thymocyte clone that induced only pro-T acute lymphoblastic leukemia, coexpression of Bcr/Abl expanded its leukemic phenotype to include acute myeloid leukemia, suggesting that unique functions of cooperating signaling oncoproteins can influence the lymphoid versus myeloid character of E2a/Pbx1 leukemia and may cooperate with E2a/Pbx1 to dictate the pre-B-cell phenotype of human leukemia containing t(1;19).
Mol Cell Biol 2004 Feb
PMID:E2a/Pbx1 induces the rapid proliferation of stem cell factor-dependent murine pro-T cells that cause acute T-lymphoid or myeloid leukemias in mice. 1472 70

The stromal cell-derived factor-1 (SDF-1) gene contains a common polymorphism, termed SDF1-3'A, in an evolutionarily conserved segment of the 3'-untranslated region (3'-UTR). We compared SDF-1 genotypes in patients diagnosed with lymphoid leukemias and lymphomas. Since the SDF1-3'A variant deletes the MspI restriction site, PCR-restriction fragment length polymorphism (RFLP) analysis was used for identification of genotypes. We identified the heterozygous genotype (3'A/wt) in 38.8% (24/62) of lymphoma patients and in 26.2% (11/42) of lymphoid leukemias. The percentage of 3'A carriers was significantly higher in lymphomas (43.5%) than in lymphoid leukemias (26.2%; P < 0.05). Our study indicates that lymphoma patients from Brazil are more likely to carry the 3'A gene than patients with lymphoid leukemias, suggesting that this polymorphism may be a differential determinant of lymphomas and lymphoid leukemia.
Blood Cells Mol Dis
PMID:Molecular investigation of the stromal cell-derived factor-1 chemokine in lymphoid leukemia and lymphoma patients from Brazil. 1522 17

Breast cancer resistance protein (BCRP) is an ATP binding cassette transporter that confers resistance to a series of anticancer agents such as 7-ethyl-10-hydroxycamptothecin (SN-38), topotecan, and mitoxantrone. In this study, we evaluated the possible interaction of gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, with BCRP. BCRP-transduced human epidermoid carcinoma A431 (A431/BCRP) cells acquired cellular resistance to gefitinib, suggesting that BCRP could be one of the determinants of gefitinib sensitivity in a certain sort of cells. Next, the effect of gefitinib on BCRP-mediated drug resistance was examined. Gefitinib reversed SN-38 resistance in BCRP-transduced human myelogenous leukemia K562 (K562/BCRP) or BCRP-transduced murine lymphocytic leukemia P388 (P388/BCRP) cells but not in these parental cells. In addition, gefitinib sensitized human colon cancer HT-29 cells, which endogenously express BCRP, to SN-38. Gefitinib increased intracellular accumulation of topotecan in K562/BCRP cells and suppressed ATP-dependent transport of estrone 3-sulfate, a substrate of BCRP, in membrane vesicles from K562/BCRP cells. These results suggest that gefitinib may overcome BCRP-mediated drug resistance by inhibiting the pump function of BCRP. Furthermore, P388/BCRP-transplanted mice treated with combination of irinotecan and gefitinib survived significantly longer than those treated with irinotecan alone or gefitinib alone. In conclusion, gefitinib is shown to interact with BCRP. BCRP expression in a certain sort of cells is supposed to be one of the determinants of gefitinib sensitivity. Gefitinib inhibits the transporter function of BCRP and reverses BCRP-mediated drug resistance both in vitro and in vivo.
Mol Cancer Ther 2004 Sep
PMID:Gefitinib reverses breast cancer resistance protein-mediated drug resistance. 1536 6


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