microcystin has been researched along with Breast-Neoplasms* in 2 studies
2 other study(ies) available for microcystin and Breast-Neoplasms
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PP1 phosphatase is involved in Bcl-2 dephosphorylation after prolonged mitotic arrest induced by paclitaxel.
During mitotic arrest induced by paclitaxel, most of the mitochondrial Bcl-2 is phosphorylated. This mitotic arrest is transient; exit from mitosis, due to mitotic slippage, occurs and Bcl-2 is rapidly dephosphorylated. In the present study, we characterized PP1 as the cytosolic phosphatase involved in Bcl-2 dephosphorylation. When mitochondria and cytosol prepared from mitotic arrested cells were incubated in vitro, the proportion of phosphorylated forms of Bcl-2 in mitochondria remained unchanged. In contrast, cytosol prepared from cells during mitotic slippage led to a dose-dependent loss of phosphorylated forms of Bcl-2. Depletion of these cytosol extracts by microcystin-Sepharose maintained Bcl-2 phosphorylated forms, indicating that this cytosol possessed phosphatase activity. Furthermore, the dephosphorylation of Bcl-2 by cytosol prepared from cells exiting mitotic block was inhibited by okadaic acid, at a dose known to inhibit PP1, and by inhibitor 2, a specific inhibitor of PP1 and by immunodepletion of PP1. Finally, we showed that PP1 is associated with mitochondrial Bcl-2 in vivo. Taken together, these results demonstrate that PP1 is directly involved in Bcl-2 dephosphorylation during mitotic slippage. Topics: Antineoplastic Agents; Breast Neoplasms; Cytosol; Enzyme Inhibitors; Female; Humans; Microcystins; Mitochondria; Mitosis; Paclitaxel; Peptides, Cyclic; Phosphoprotein Phosphatases; Phosphorylation; Precipitin Tests; Protein Binding; Proto-Oncogene Proteins c-bcl-2; Sepharose; Tumor Cells, Cultured | 2002 |
Protein kinase C epsilon translocation and phosphorylation by cis-diamminedichloroplatinum(II) (CDDP): potential role in CDDP-mediated cytotoxicity.
Phorbol ester-like protein kinase C (PKC) activators, such as 12-O-tetradecanoylphorbol-13-acetate, and perturbation of some growth factor receptors have been reported to alter the cytotoxicity of cis-diamminedichloroplatinum(II) (CDDP). To study the mechanism of this alteration, we have examined the effect of CDDP per se on PKC isozymes. The SKBR-3 human breast carcinoma cell line exhibits at least six different PKC isozymes (PKC alpha, betaI, betaII, delta, epsilon, and zeta). After exposure to 10-100 microM CDDP for 3 h, only PKC epsilon translocated from the plasma membrane to the nuclear membrane and to the cytosolic fraction. This translocation was observed in a time- and dose-dependent manner by Western blot and confocal microscopy. CDDP also decreased the mobility of PKC epsilon in the nuclear membrane fraction, an effect that was blocked by protein phosphatase 2A, suggesting drug-mediated isozyme phosphorylation. This translocation and phosphorylation were also induced by the cisplatin analogue carboplatin but not with the anticancer agents Adriamycin and Taxol. Antisense oligodeoxynucleotides against PKC epsilon down-regulated isozyme content, blocked drug-induced translocation, and reduced cisplatin-mediated cytotoxicity 3-fold compared to that of sense-treated cells. Antisense PKC epsilon also decreased SKBR-3 cell sensitivity to carboplatin but not to Adriamycin and Taxol. These data support a role for PKC epsilon translocation and phosphorylation on CDDP-mediated toxicity. Topics: Antineoplastic Agents; Biological Transport; Breast Neoplasms; Carboplatin; Carcinoma; Cisplatin; Cytosol; DNA Fragmentation; Enzyme Activation; Enzyme Inhibitors; Humans; Isoenzymes; Microcystins; Nuclear Envelope; Oligonucleotides, Antisense; Peptides, Cyclic; Phosphoprotein Phosphatases; Phosphorylation; Protein Kinase C; Protein Kinase C-epsilon; Protein Phosphatase 2; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured | 1998 |