• Corpus ID: 19996844

Prevention of phorbol ester receptor down modulation in human myeloblastic leukemia ML-1 cells by differentiation-stimulating serum components.

  title={Prevention of phorbol ester receptor down modulation in human myeloblastic leukemia ML-1 cells by differentiation-stimulating serum components.},
  author={Hirofumi Sakagami and Rosemary Hromchak and Andreas Block},
  journal={Cancer research},
  volume={44 8},
The phorbol esters 12-O-tetradecanoylphorbol-13-acetate, phorbol 12,13-didecanoate, phorbol 12,13-dibutyrate (PDB), and phorbol 12,13-dibenzoate were found to compete with [20-3H]-PDB binding to human myeloblastic leukemia ML-1 cells in approximate proportion to their differentiation-inducing capacity. Fetal bovine serum decreased the down modulation of phorbol ester receptor sites on these cells and increased PDB-induced differentiation. These two activities coeluted upon chromatography of… 

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A phorbol diester resistant monocytic leukemia cell line is PKC deficient.

This cell line provides a new system for studying the signal transduction mechanisms in induced monocytic differentiation and demonstrates that MIA C51 cells contained significantly lower number of PDBu receptors, protein kinase C activity, and PKC protein level.

Changes in isoenzyme profiles during induction of differentiation in human myelomonocytic leukemia cell lines.

Differentiation of nonmonocytoid cells appears, at the isoenzyme level, to be quite different from that of the monocy toid cell lines.

Mechanism of interaction between antineoplastic agents and natural differentiation factors in the induction of human leukemic cell maturation.

Results indicate that the drug sensitizes the cells to respond to concentrations of CM to which they would otherwise be refractive, and the drug-induced sensitization is reversible.

Lipoprotein modulation of the intracellular localization of protein kinase C and alteration of phorbol ester-stimulated differentiation in the human monoblastic U937 cell line.

It is suggested that serum lipoproteins modulate protein kinase C localization and the response to phorbol ester stimulation in the U937 cell, which is similar to that observed with 5% fetal bovine serum.

Differentiation-induced ML-1 cells as targets for transformation by a chemical carcinogen.

Differentiation-uninduced ML-1 cells do not respond to treatment with N-nitroso-N-methylurea, indicating that differentiation-induced cells, at an early stage of the maturation process, may be the targets for the carcinogen-mediated transformation.

Declined asparagine synthetase mRNA expression and enhanced sensitivity to asparaginase in HL-60 cells committed to monocytic differentiation.

During 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced differentiation of human promyelocytic leukemia HL-60 cells toward maturing monocytes/macrophages, asparagine synthetase (ASNS) mRNA expression declined time and dose-dependently, suggesting the possible involvement of MEK1/2 MAPK in the inhibitory effect of TPA on ASNS mRNA expression.



Down regulation of specific binding of [20-3H]phorbol 12,13-dibutyrate and phorbol ester-induced differentiation of human promyelocytic leukemia cells.

The results indicate that the down regulation of specific [3H]PDB binding may be a crucial early event in the control of phorbol ester-induced terminal differentiation in HL-60 cells and suggest that such down regulation may be involved in other cellular and biochemical effects ofphorbol diester tumor promoters.

Phorbol ester induction of leukemic cell differentiation is a membrane-mediated process.

It is demonstrated that phorbol esters exert their effects while retained at the cell surface through the stimulation of phosphatidylcholine synthesis, which appears to be a part of a receptor-mediated, transmembrane process.

Characterization of phorbol ester receptors and their down-modulation in GH4C1 rat pituitary cells.

A distinctive new finding is the down modulation of phorbol ester binding sites on GH4C1 cells by both homologous and heterologous ligands, which may represent a mechanism for attenuating cellular responsiveness to ph orbol esters in their continued presence.

Association of phorbol ester receptor down modulation with a cryptic receptor state.

Comparison of receptor properties in cells and lysates and down modulation suggest that the affinity and ligand specificity of the phorbol ester receptor may depend on its cellular environment.

Inhibition of phorbol ester-receptor binding by a factor from human serum

The results indicate that the serum factor inhibits [3H]PDBu binding by a direct physical effect at the level of the phorboid receptors or their associated membranes.

Specific binding of phorbol ester tumor promoters to intact primary epidermal cells from Sencar mice.

  • V. SolankiT. Slaga
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1981
Epidermal cells exposed to retinoic acid or fluocinolone acetonide for 24 hr had similar [3H]PDB binding characteristics as untreated cells suggesting that inhibition of tumor promotion induced by these compounds is not mediated through alterations in the phorbol ester binding sites.

Identification of receptors for phorbol ester tumor promoters in intact mammalian cells and of an inhibitor of receptor binding in biologic fluids.

An assay for high-affinity phorbol ester receptors in intact rat embryo fibroblasts is developed and the tumor promoters 12-O-tetradecanoyl-phorbol 13-acetate, teleocidin B, and mezerein were potent inhibitors of [3H]P(Bu)2 binding.

Kinetics of appearance of differentiation-associated characteristics in ML-1, a line of human myeloblastic leukemia cells, after treatment with 12-O-tetradecanoylphorbol-13-acetate, dimethyl sulfoxide or 1-beta-D-arabinofuranosylcytosine.

The data show that the same differentiation-associated characteristics were caused to be expressed by the three chemical agents at different rates and to different extents, reflecting the differences in their ability to induce morphological maturation.

Modulation of T leukaemic cell phenotype with phorbol ester

A panel of monoclonal antibodies and other markers have been used in conjunction with flow cytometry and biochemical analysis to monitor the induction of maturation in human thymic (T) leukaemic cell lines by phorbol ester (TPA) and provide support for the view that leukaemia may involve regulatory defects in the coupling of proliferation and maturation.

Phorbol ester-induced differentiation of a non-T, non-B leukemic cell line: model for human lymphoid progenitor cell development.

Results show clearly that TPA is capable of inducing phenotypic changes in REH cells, which may reflect the differentiation-linked expression of antigens present in normal bone marrow lymphoid progenitor cells.