| Abstract: |
Basic fibroblast growth factor (bFGF) is a pleiotropic cytokine which has recently been shown to delay fludarabine-induced apoptosis in B cell chronic lymphocytic leukemia (B-CLL) cells. To investigate the potential mechanism of bFGF-mediated delay of apoptosis, two EBV-transformed B prolymphocytic cell lines (JVM-2, JVM-13), one EBV-transformed B-CLL cell line (183CLL), and one non-EBV-transformed B-CLL cell line (WSU-CLL) were used as a model for chronic lymphoid malignancies. Viability data of cells treated with fludarabine alone or in combination with bFGF demonstrated that the addition of bFGF to the cells resulted in prolonged survival. Quantitative assessment of apoptosis-associated DNA strand breaks by in situ TdT labeling showed a protective effect of bFGF on fludarabine-treated cells. The potential effect of bFGF on bcl-2 mRNA expression was analyzed by Northern blotting. Stimulation with bFGF led to a time-dependent accumulation of bcl-2 specific mRNA in all three cell lines. Maximal levels of bcl-2 mRNA expression were detected after 8 h in JVM-2, and after 18 h in JVM-13 and 183CLL. Intracellular bcl-2 protein was also found to be increased upon bFGF stimulation in both EBV- and non-EBV-transformed cells. In addition, exposure of cells from three patients with B-CLL to bFGF showed an upregulation of bcl-2 protein after 4-8 h. Our data demonstrate that bFGF upregulates the expression of bcl-2 in these cells, suggesting that this increase in bcl-2 expression may play a role in the delay of fludarabine-induced apoptosis. |
| Keywords: |
controlled study; human cell; fludarabine; protein bcl 2; apoptosis; neoplasm proteins; tumor cells, cultured; b-lymphocytes; dna strand breakage; fibroblast growth factor 2; messenger rna; rna, messenger; dactinomycin; protein induction; cell line, transformed; gene induction; drug cytotoxicity; chronic lymphatic leukemia; rna, neoplasm; proto-oncogene proteins c-bcl-2; epstein barr virus; vidarabine; leukemia cell line; gene expression regulation, leukemic; northern blotting; b cell leukemia; bcl-2; dna fragmentation; chronic lymphocytic leukemia; basic fibroblast growth factor; humans; human; priority journal; article; virus cell transformation; leukemia, b-cell, chronic
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