Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

B-cell chronic lymphocytic leukemia (CLL) is a clonal B cell malignancy of morphologically mature, functionally immature B cells. B-cell CLL cells are known to be resistant to killing by anticancer and other agents. This resistance is associated with alterations in apoptosis and cell cycle regulated genes. In our earlier studies, we have demonstrated that CLL cells have differential expression of genes that are associated with apoptosis and cell cycle regulation, including elevated expression of Bcl-2, DAD-1, Cyclin D3 and cyclin dependent kinase 4 inhibitor. Therefore, in this study, in an attempt to study the role of Cyclin D3 in the resistant behavior of CLL cells, Cyclin D3 was down regulated using antisense oligonucleotide (AS-ODN) in WSU-CLL, a human CLL cell line. The down regulation of Cyclin D3 was confirmed by RT-PCR and flow cytometry techniques. The Cyclin D3 expression down-regulated WSU-CLL cells were then tested for their susceptibility to fludarabine, a chemotherapeutic agent. Our results showed that the Cyclin D3 expression down-regulated WSU-CLL cells were more susceptible to fludarabine mediated killing. Following treatment with fludarabine, there was a significant increase in the number of cells undergoing apoptosis in Cyclin D3 expression down-regulated WSU-CLL cells as determined by Annexin-V assay, cell cycle analysis for DNA content, and cytomorphology. Thus, our results indicate Cyclin D3 down regulation increases the killing of WSU-CLL cells with fludarabine by increasing the number of cells undergoing apoptosis.
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PMID:Increased apoptosis in B-chronic lymphocytic leukemia cells as a result of cyclin D3 down regulation. 1268 40

Until recently, the lack of molecular probes hampered the determination of the expression of pro-apoptotic and anti-apoptotic genes in sponge. In an approach to solve this problem, the present study describes a variety of cDNAs from the demosponge Suberites domuncula, coding for proteins that are characteristic for the initiation of apoptosis (caspase, MA3, ALG-2 protein), for the prevention of programmed cells death (2 Bcl-2 homology proteins, FAIM-related polypeptide, and DAD-1-related protein), and for morphogenetic processes (retinoid X receptor). They were used as probes to monitor the expression levels in vitro in the allogeneic mixed sponge cell reaction (MSCR) system. In the allogeneic MSCR, two-cell aggregates (primmorphs) from genetically different animals of the same species were positioned next to each other. After approximately 8 days in culture, one of the primmorphs underwent apoptotic death, while the second remained alive. The expression levels of the aforementioned genes were determined by Northern blotting and by in situ hybridization. These experiments revealed that in the apoptotic primmorph, the characteristic apoptotic genes were expressed, while in the non-apoptotic aggregates the cell-survival genes are highly upregulated. Interestingly, the transcript levels of retinoid X receptor were higher in apoptotic primmorphs than in the non-apoptotic aggregate in the assay. Our data show for the first time that in the in vitro MSCR system, allogeneic recognition led to apoptotic cell death in one partner, while the other one survived. We suggest that this process is controlled by a differential expression of the pro-apoptotic and pro-survival genes studied here.
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PMID:Allograft rejection in the mixed cell reaction system of the demosponge Suberites domuncula is controlled by differential expression of apoptotic genes. 1551 43