Phorbol esters induce death in MCF-7 breast cancer cells with altered expression of protein kinase C isoforms. Role for p53-independent induction of gadd-45 in initiating death
| Autor: | George J. Pettit, Guillermina Lozano, Donald J. Fletcher, Winifred O. Bryant, Jianming Chen, D. Kirk Ways, Paul P. Cook, Cynthia A. Kukoly, James E. De Vente, Peter J. Parker, Karla J. Posekany |
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| Jazyk: | angličtina |
| Rok vydání: | 1995 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Bryostatin 1 Apoptosis Breast Neoplasms Biology Retinoblastoma Protein Lactones Cyclins Tumor Cells Cultured Cytotoxic T cell Humans Phosphorylation skin and connective tissue diseases Protein kinase C Protein Kinase C Dose-Response Relationship Drug Gadd45 Cell Cycle Retinoblastoma protein Intracellular Signaling Peptides and Proteins Proteins General Medicine Cell cycle Bryostatins Genes p53 Isoenzymes Tetradecanoylphorbol Acetate Cancer research biology.protein Female Macrolides Research Article |
| Popis: | Protein kinase C (PKC) modulates growth, differentiation and apoptosis in a cell-specific fashion. Overexpression of PKC-alpha in MCF-7 breast cancer cells (MCF-7-PKC-alpha cell) leads to expression of a more transformed phenotype. The response of MCF-7 and MCF-7-PKC-alpha cells to phorbol esters (TPA) was examined. TPA-treated MCF-7 cells demonstrated a modest cytostatic response associated with a G1 arrest that was accompanied by Cip1 expression and retinoblastoma hypophosphorylation. While p53 was detected in MCF-7 cells, evidence for TPA-induced stimulation of p53 transcriptional activity was not evident. In contrast, TPA treatment induced death of MCF-7-PKC-alpha cells. Bryostatin 1, another PKC activator, exerted modest cytostatic effects on MCF-7 cells while producing a cytotoxic response at low doses in MCF-7-PKC-alpha cells that waned at higher concentrations. TPA-treated MCF-7-PKC-alpha cells accumulated in G2/M, did not express p53, displayed decreased Cip1 expression, and demonstrated a reduction in retinoblastoma hypophosphorylation. TPA-treated MCF-7-PKC-alpha cells expressed gadd-45 which occurred before the onset of apoptosis. Thus, alterations in the PKC pathway can modulate the decision of a breast cancer cell to undergo death or differentiation. In addition, these data show that PKC activation can induce expression of gadd45 in a p53-independent fashion. |
| Databáze: | OpenAIRE |
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