Antisense src Expression Inhibits U937 Human Leukemia Cell Proliferation in Conjunction with Reduction of c-myb Expression

Waki, Masato; Kitanaka, Akira; Kamano, Hiroshi; Tanaka, Tadashi; Kubota, Yukiho; Ohnishi, Hideki; Takahara, Jiro; Irino, Shozo

doi:10.1006/bbrc.1994.1801

Cited by 9 publications

(10 citation statements)

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“…These cells were noted to have decreased Bcl-2 (an anti-apoptotic protein) promoter activity and protein levels, which imply that c-Myb was needed to block the signalling mechanisms that committed the cells to apoptosis (Yi et al, 2002;Taylor et al, 1996). Furthermore, anti-sense mRNA treatment used to ablate c-Myb expression also decreased the life span of leukemic cells (Kitanaka et al, 1994;Waki et al, 1994). These results suggest that c-Myb also plays an important role in apoptosis.…”

Section: C-mybmentioning

confidence: 93%

The effects of 1,4-benzoquinone on c-Myb and topoisomerase II in K-562 cells

Singh

Winn

2008

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Exposure to benzene, a ubiquitous environmental pollutant, has been linked to leukemia, although the mechanism of benzene-initiated leukemogenesis remains unclear. Benzene can be bioactivated to toxic metabolites such as 1,4 benzoquinone (BQ), which can alter signaling pathways and affect chromosomal integrity. BQ has been shown to increase the activity of c-Myb, which is an important transcription factor involved in hematopoiesis, cell proliferation, and cell differentiation. The c-Myb protein has also been shown to increase topoisomerase IIalpha (Topo IIalpha) promoter activity specifically in cell lines with hematopoietic origin. Topo IIalpha is a critical nuclear enzyme that removes torsional strain by cleaving, untangling and religating double-stranded DNA. Since Topo IIalpha mediates DNA strand breaks, aberrant Topo IIalpha activity or increased protein levels may increase the formation of DNA strand breaks, leaving the cell susceptible to mutational events. We hypothesized that BQ can increase c-Myb activity, which in turn increases Topo IIalpha promoter activity resulting in increased DNA strand breaks. Using luciferase reporter assays in K-562 cells we demonstrated that BQ (25 and 37microM) exposure caused an increase in c-Myb activity after 24h. Contradictory to previous findings, overexpression of exogenous c-Myb or a polypeptide consisting of c-Myb's DNA binding domain (DBD), which competitively inhibits the binding of endogenous c-Myb to DNA, did not affect Topo IIalpha promoter activity. However, BQ (37microM for 24h) exposure caused a significant increase in Topo IIalpha promoter activity, which could be blocked by the overexpression of the DBD polypeptide, suggesting that BQ exposure increases Topo IIalpha promoter activity through the c-Myb signaling pathway.

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Section: C-mybmentioning

confidence: 93%

The effects of 1,4-benzoquinone on c-Myb and topoisomerase II in K-562 cells

Singh

Winn

2008

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…Proteins were separated by using 10% SDS‐PAGE and electrophoretically transferred to polyvinylidene difluoride (PVDF) membrane (Micron Separations Inc.; Westboro, MA). Immunoblot analysis using antiphosphotyrosine monoclonal antibody (αPY mAb; Sigma) was performed as described previously [11]. Protein bands were visualized by using an enhanced chemiluminescence system (Amersham; Backinghamshire, England).…”

Section: Methodsmentioning

confidence: 99%

“…Platelets were lysed with the lysis buffer containing 1% Triton X‐100 [11] after treatment with TPO, ADP and genistein as described above. Then the cell lysates were immunoprecipitated with anti‐p44MAPI‐kinase (αERK1) PcAb (Santa Cruz Biotechnology Inc.; Santa Cruz, CA).…”

Section: Methodsmentioning

confidence: 99%

Thrombopoietin Modulates Platelet Activation in Vitro through Protein‐Tyrosine Phosphorylation

et al. 1996

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Abstract. To determine the roles of thrombopoietin (TPO) in platelet function in vitro, we examined the effects of TPO on platelet aggregation. Although several proteins in platelets were tyrosine-phosphorylated by TPO treatment, TPO alone was unable to induce platelet aggregation. However, the secondary wave of platelet aggregation induced by adenosine diphosphate (ADP) was enhanced by TPO in a dose-dependent manner. TPO in conjunction with ADP augmented tyrosine phosphorylation of platelet proteins, including tyrosine-phosphorylated proteins induced by TPO alone. Genistein inhibited protein-tyrosine phosphorylation in platelets induced by TPO with ADP and suppressed TPO-enhanced platelet aggregation. Moreover, tyrosine phosphorylation of MAPkinases induced by TPO alone and TPO with ADP was consistent with TPO-enhanced platelet aggregation. These findings in the present study suggest that signal transduction involved in TPO-enhanced platelet aggregation is mediated in part by tyrosine-phosphorylated proteins, including MAPkinases, in platelets through TPO-stimulated c-Mpl, TPO receptor.

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“…5 In particular, the nonreceptor pp60c-Src PTK transduces signals that control the above cellular processes. [6][7][8] Src is activated following engagement of many different classes of cellular receptors and participates as a convergence point in different signaling pathways. 3;4;9 In this regard, Src is a critical component of the signaling cascades initiated by tyrosine kinase-linked receptors, such as the epidermal growth factor receptor (EGFR), and Gprotein coupled receptors and is directly associated with, and may regulate signaling via, the EGFR and HER-2/ neu receptor PTKs, 10;11 both of which are involved in cancer.…”

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confidence: 99%