Bryostatin 1 activates protein kinase C and induces monocytic differentiation of HL-60 cells

Stone, RM; Sariban, Eric; Pettit, GR; Kufe, DW

doi:10.1182/blood.v72.1.208.bloodjournal721208

Cited by 20 publications

(17 citation statements)

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“…To determine if the differences in E2F binding and pRb phosphorylation affected downstream gene transcription, the product of one of the targets of E2F, the c-myc oncogene, was monitored. In concordance with previous reports of c-myc regulation in HL-60 cells [9,28,43], PMA treatment of U937 cells decreased c-Myc expression to 40% by 12 h and <1% of control levels by 24 h (Fig. 7).…”

Section: Differential Regulation Of Rb Phosphorylation and E2f Bindinsupporting

confidence: 93%

“…However, its spectrum of activity is distinct from that of phorbols, and it blocks those phorbol-associated activities that it does not possess [24,27,42]. In human promyelocytic leukemia cells (HL-60), bryostatin 1 variably induces maturation [29,43]; moreover, it blocks PMA effects in sublines immune to its differentiation-inducing actions [27]. In the human monocytic leukemic cell line U937, bryostatin 1 has been reported to exert antiproliferative effects by some investigators [4], although others have found its activity to be marginal, and consistently less than that exerted by PMA [7,36].…”

Section: Introductionmentioning

confidence: 99%

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Divergent effects of bryostatin 1 and phorbol myristate acetate on cell cycle arrest and maturation in human myelomonocytic leukemia cells (U937)

Vrana¹,

Saunders²,

Chellappan

et al. 1998

Differentiation

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Section: Differential Regulation Of Rb Phosphorylation and E2f Bindinsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Divergent effects of bryostatin 1 and phorbol myristate acetate on cell cycle arrest and maturation in human myelomonocytic leukemia cells (U937)

Vrana¹,

Saunders²,

Chellappan

et al. 1998

Differentiation

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“…This increase in DNA binding occurs prior to increases in CAT activity, which may reflect the need for transcription and translation of the mRNA. The addition of okadaic acid, a phosphatase inhibitor, and bryostatin 1, a non-phorbol ester activator of PKC, to U937 cells stimulates the differentiation of these cells to macrophages (Adunyah et al, 1992;Kraft et al, 1987;Stone et al, 1988). Both of these agents activate transcription from the AP-1 enhancer element and stimulate increases in c-myc mRNA, protein, and phosphorylation.…”

Section: Ap-3 But Not the Ap-2 Enhancer Sequence Is Functional Duringmentioning

confidence: 99%

Regulation of AP‐3 enhancer activity during hematopoietic differentiation

Adler

Kraft

1995

Journal Cellular Physiology

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Phorbol ester treatment of the human leukemic cell line U937 induces macrophage differentiation over 24-48 hr. This differentiation is mediated by the activation and/or repression of specific gene transcription by proteins, enhancer binding factors, that bind to the DNA upstream of the start site of transcription. We find that differentiation of U937 cells induced by phorbol esters and bryostain 1, activators of protein kinase C, and the phosphatase inhibitor, okadaic acid, stimulates transcription from an enhancer sequence which contains multimerized AP-3 binding sequences but not from one that contains multimerized AP-2 binding motifs. Electrophoretic mobility shift assays (EMSA) demonstrate that AP-3 DNA binding activity peaks at 24 hr, remains elevated for 24 hr, and then decreases thereafter. Southwestern blotting demonstrates that the AP-3 enhancer sequence binds to a 48 kDa protein present in these leukemic cells. Because the AP-3-oligomer also contains an overlapping NF-kappa B-like site, the role of NK-kappa B proteins in regulating transcription from this multimerized oligonucleotide was investigated. Transfection of U937 cells with NF-kappa B family members demonstrated activation of AP-3-mediated transcription by rel A but little effect induced by NFKB1 and c-rel. It is unlikely, however, that phorbol ester-induced transcription from this AP-3 sequence is solely mediated by this NF-kappa B family member since treatment of U937 cells with antisense rel A oligodeoxynucleotides did not block phorbol ester-mediated transcription from the AP-3 site. These data demonstrate that AP-3, but not AP-2 sequences, functions to activate mRNA transcription during phorbol ester-induced hematopoietic differentiation and suggests a complex interaction between NF-kappa B and AP-3 proteins in the regulation of this enhancer element.

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“…Cytocentrifuge smears of cultured cells were examined for NSE staining (Yam et al, 1971). Expression of the Mac-1 cell surface antigen was quantitated by flow cytometry using monoclonal antibodies (MAb) LM2il and OKMl (Stone et al, 1988;Miller et al, 1986).…”

Section: Induction Of Differentiationmentioning

confidence: 99%

Effects of dexamethasone on induction of monocytic differentiation in human U‐937 cells by dimethylsulfoxide

Nakamura

Kharbanda

Spriggs

et al. 1990

Journal Cellular Physiology

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The present studies demonstrate that dimethylsulfoxide (DMSO) treatment of human U-937 myelomonocytic leukemia cells is associated with induction of monocytic differentiation. The DMSO-induced U-937 monocytic phenotype was associated with 1) growth inhibition, 2) loss of clonogenic survival, 3) increases in alpha-naphthyl acetate esterase (NSE) staining, and 4) increases in cell surface expression of the monocyte marker Mac-1. DMSO treatment of U-937 cells was also associated with down-regulation of c-myc and c-myb gene expression as well as with increases in tumor necrosis factor (TNF) mRNA levels. The results further demonstrate that induction of U-937 monocytic differentiation by DMSO is accompanied by increases in phospholipase A2 activity. Moreover, this stimulation of phospholipase A2 was sensitive to dexamethasone. We therefore studied the effects of dexamethasone on DMSO-induced differentiation of U-937 cells. Although dexamethasone had no effect on growth inhibition or loss of clonogenic survival by DMSO, this glucocorticoid blocked increases in NSE staining and cell surface Mac-1 expression. Dexamethasone also had no effect on the down-regulation of c-myc and c-myb expression but blocked the reappearance of c-myb transcripts after 6 hr of DMSO treatment. Finally, dexamethasone inhibited DMSO-induced increases in TNF gene expression. Taken together, the results demonstrate that dexamethasone inhibits multiple characteristics, including the stimulation of phospholipase A2 activity, associated with DMSO-induced monocytic differentiation of U-937 cells.

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Bryostatin 1 activates protein kinase C and induces monocytic differentiation of HL-60 cells

Cited by 20 publications

References 0 publications

Divergent effects of bryostatin 1 and phorbol myristate acetate on cell cycle arrest and maturation in human myelomonocytic leukemia cells (U937)

Divergent effects of bryostatin 1 and phorbol myristate acetate on cell cycle arrest and maturation in human myelomonocytic leukemia cells (U937)

Regulation of AP‐3 enhancer activity during hematopoietic differentiation

Effects of dexamethasone on induction of monocytic differentiation in human U‐937 cells by dimethylsulfoxide

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