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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reviews the information concerning immunological memory T and B cells. It shows that the existence of different or a single lineage of memory and naive cells is still a question. The recirculation pattern of memory cells is different from naive cells. A unique recirculation for memory T or B cells is suggested while the bcl2 gene expression possibly plays role in the longevity of memory cells. Various phenotypic markers are demonstrated only on memory or on naive cells; however, a reliable and convenient method for the detection of memory cells still needs to be explored.
Asian Pac J Allergy Immunol 1995 Jun
PMID:Characterization of immunological memory cells. A minireview. 748 49

The Bcl-2 homologue, Bak, is a potent inducer of apoptosis. FISH data presented here located the gene to 6p21.3. Mapping was consistent with its location centromeric of the HSET locus and approximately 400kb from the MHC. The construction of a contig of genomic clones across the locus facilitated the sequencing of a PAC containing the gene. Comparison of the gene structure to functional and physical domains revealed a good agreement between the physical structure and the intron-exon organisation. The position of a single intron was conserved in comparison to other members of the Bcl-2 family, namely Bax, CED-9, Bcl-X and Bcl-2, but all other introns were displaced, consistent with a divergent phylogeny.
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PMID:Genomic structure and domain organisation of the human Bak gene. 957 42

The anti-cancer drug taxol is known to bind to and induce the polymerization of tubulin and has recently been shown to bind to the anti-apoptotic protein Bcl-2, but not to its homolog, Bcl-XL. Libraries of random peptides displayed on the surface of a bacteriophage were screened to select those exhibiting affinity for taxol. The sequences of these peptides were compared to sequences of proteins involved in mitosis and apoptosis. No significant similarities were detected between the sequences of tubulins and the taxol-selected peptides. However, a high level of similarity exists between the selected peptides and the disordered loop of Bcl-2. Conversely, there was little similarity between the sequences of the selected peptides and Bcl-XL. These results indicate that peptides displayed on the surface of a bacteriophage can mimic the ligand-binding behavior of a disordered protein loop and that comparison of the sequences of affinity-selected peptides with protein sequences can be predictive for ligand binding.
Pac Symp Biocomput 1999
PMID:Similarity between the sequences of taxol-selected peptides and the disordered loop of the anti-apoptotic protein, Bcl-2. 1038 Feb 25

The beclin 1 (BECN1) gene encodes a 60-kDa coiled-coil protein that interacts with the prototypic apoptosis inhibitor Bcl-2. Previous studies indicate that beclin 1 maps to a region approximately 150 kb centromeric to BRCA1 on chromosome 17q21 that is commonly deleted in breast, ovarian, and prostate cancer. The complete cDNA sequence of beclin 1 encodes a 2098-bp transcript, with a 120-bp 5' UTR, 1353-bp coding region, and 625-bp 3' UTR. Hybridization screening of a human genomic PAC library identified PAC 452O8, which contains the complete beclin 1 gene. Determination of the exon-intron structure of beclin 1 reveals 12 exons, ranging from 61 to 794 bp, which extend over 12 kb of the human genome. FISH analysis of human breast carcinoma cell lines using PAC 452O8 as probe identified allelic beclin 1 deletions in 9 of 22 cell lines. Sequencing of genomic DNA from 10 of these cell lines revealed no mutations in coding regions or splice junctions. Additionally, Northern blot analysis of 11 cell lines did not identify any abnormalities in beclin 1 transcripts. These results indicate that human breast carcinoma cell lines frequently contain allelic deletions of beclin 1, but not beclin 1 coding mutations.
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PMID:Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. 1039

Few studies have referred to the implication of apoptotic processes following hormonal treatment. No data are available on the effects of progesterone in breast cells. In order to gain insights on the effects of the gonadal steroids and antiestrogens in breast cells, we have carried out studies on apoptosis in different breast materials. We have developed a model of normal breast cells in cultures that remain hormone-dependent. On these cells and in some hormone-dependent breast cancer cell lines (T-47-D, ZR75-1, MCF-7) we have observed an antiapoptotic effect of estradiol (E(2)) and a potent proapoptotic effect of some antiestrogens. Progestins were also proapoptotic in normal as well as in hormone-dependent breast cancer cells. In order to understand the mechanisms of these hormones on apoptosis, we studied the bcl-2 family proteins. We demonstrated that E(2) increased the antiapoptotic proteins, bcl-2 and bclx(L), whereas, the progestins drastically decreased bcl-2 expression and weakly bclx(L) levels. We investigated the mechanisms by which E(2) increased bcl-2 expression. Our results using quantitative RT-PCR showed that E(2) increased bcl-2 mRNA levels at 48 h of treatment via a transcriptional mechanism. None of the hormone treatments altered the proapoptotic protein levels, bax and bak. We also studied the in vivo expression of bcl-2 and other members of its family in biopsies of normal breast tissues according to the menstrual cycle. Bcl-2 displayed a strong cyclical variation and seemed to be the most hormone-dependent member of the family.
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PMID:Hormonal regulation of apoptosis in breast cells and tissues. 1110 64

Lung cancer is a complex group of diseases but each lesion is thought to originate from a single mutated progenitor cell. It is evident that multiple genetic changes are involved in the generation of each specific type of lung cancer. Due to the high complexity of these processes and rapid metastasis, treatment of advanced lung cancer, particularly of NSCLCs, is far from satisfactory. Thus, there is a need for innovative strategies for modulation of adverse alteration in protooncogene or tumor suppressor genes so that lung carcinogenesis can be suppressed or delayed. To this end, we have evaluated the effects of tea compounds (theaflavins, epicatechin-gallate and epigallo-catechin-gallate) on proliferation and apoptosis and associated gene expression in a highly metastatic human lung cancer cell line NCI-H460. Significant reduction of cell proliferation, detected in situ by BrdU incorporation, and induction of apoptosis, assessed by the by the TUNEL method, were noted following treatments. Expression of p53, Bcl-2, c-Myc and H-Ras, was localized by immunocytochemistry and analysed by Western blotting. Tea compounds upregulated expression of p53, downregulated expression of Bcl-2 but there was no significant influence on H-ras and c-Myc expressions. It is suggested that tea compounds can influence genetic alteration to disfavour, growth and survival of lung cancer cells.
Asian Pac J Cancer Prev
PMID:Inhibition of growth, induction of apoptosis and alteration of gene expression by tea polyphenols in the highly metastatic human lung cancer cell line NCI-H460. 1623 94

Induction of apoptosis is one of the most active strategies in cancer chemoprevention and the ability of medicinal plants in this regard has attracted major research interest. The present study was designed to investigate the apoptosis inducing capacity of an ethanolic neem leaf extract (ENLE) during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis using the apoptosis-associated proteins Bcl-2, Bim, caspase 8 and caspase 3 as markers. Topical application of DMBA to the hamster cheek pouch for 14 weeks resulted in well developed squamous cell carcinomas associated with increased expression of Bcl-2 and decreased expression of Bim, caspase 8 and caspase 3. Administration of ENLE inhibited DMBA-induced hamster buccal pouch (HBP) carcinogenesis, as revealed by the absence of neoplasms, with induction of Bim and caspases 8 and 3 and inhibition of Bcl-2 expression. Our results suggest that the chemopreventive effects of ENLE may be mediated by induction of apoptosis.
Asian Pac J Cancer Prev
PMID:Ethanolic neem (Azadirachta indica) leaf extract induces apoptosis in the hamster buccal pouch carcinogenesis model by modulation of Bcl-2, Bim, caspase 8 and caspase 3. 1643 3

Apoptosis and the genes regulating this process have recently become a focus of interest in the study of cancer development and progression. Both Bcl-2 and Bax are transcriptional targets for the tumor supressor protein, p53, which induces cell cycle arrest or apoptosis in response to DNA damage. The coordinate performance of these molecules is crucial for controlling life or death of a cell. Correlations between apoptosis and protein expression of genes controlling this process including Bcl-2, Bax and p53 in gastric cancer were here investigated with gastric tumor samples of forty patients . DNA ploidy pattern was analyzed using flow cytometry and Bcl-2, Bax, and p53 were immunohistochemically localized using specific monoclonal antibodies. In addition, serum Bcl-2 protein was estimated by enzyme linked immunosorbant assay (ELISA). The obtained data showed that the mean serum Bcl-2 protein concentration demonstrated a significant increase (P<0.0001) in positive cases (61.5+/-11.0 unit/ml) compared to the negative ones (47.5+/-3.5 unit/ml). Serum Bcl-2 protein positivity was detected in 13/40 of gastric cancer patients. Immunohistochemical positivity for Bcl-2, Bax, and p53 was shown in 45%, 68%, and 63% of samples, respectively. Positive Bcl-2 and p53 immunostaining was significantly linked with the histological grade (P<0.02 and P<0.009 respectively) and lymph duct invasion (P<0.02 and P<0.001 ). On the other hand, Bax was significantly differed with lymph duct invasion and the ploidy pattern (P<0.03 and P<0.002). In conclusion, the apoptosis-related genes p53, Bcl-2, and Bax are all linked to the occurrence of gastric cancer. Therefore, analysis of their expressions may add useful information concerning tumor behavior.
Asian Pac J Cancer Prev
PMID:Apoptosis dysregulation in human gastric carcinomas: relationship to anti- and pro-apoptotic protein expression. 1747 70

The intracellular signaling pathways mediating the neurotrophic actions of pituitary adenylate cyclase-activating polypeptide (PACAP) were investigated in human neuroblastoma SH-SY5Y cells. Previously, we showed that SH-SY5Y cells express the PAC(1) and VIP/PACAP receptor type 2 (VPAC(2)) receptors, and that the robust cAMP production in response to PACAP and vasoactive intestinal peptide (VIP) was mediated by PAC(1) receptors (Lutz et al. 2006). Here, we investigated the ability of PACAP-38 to differentiate SH-SY5Y cells by measuring morphological changes and the expression of neuronal markers. PACAP-38 caused a concentration-dependent increase in the number of neurite-bearing cells and an up-regulation in the expression of the neuronal proteins Bcl-2, growth-associated protein-43 (GAP-43) and choline acetyltransferase: VIP was less effective than PACAP-38 and the VPAC(2) receptor-specific agonist, Ro 25-1553, had no effect. The effects of PACAP-38 and VIP were blocked by the PAC(1) receptor antagonist, PACAP6-38. As observed with PACAP-38, the adenylyl cyclase activator, forskolin, also induced an increase in the number of neurite-bearing cells and an up-regulation in the expression of Bcl-2 and GAP-43. PACAP-induced differentiation was prevented by the adenylyl cyclase inhibitor, 2',5'-dideoxyadenosine (DDA), but not the protein kinase A (PKA) inhibitor, H89, or by siRNA-mediated knock-down of the PKA catalytic subunit. PACAP-38 and forskolin stimulated the activation of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAP; p38 MAP kinase) and c-Jun N-terminal kinase (JNK). PACAP-induced neuritogenesis was blocked by the MEK1 inhibitor PD98059 and partially by the p38 MAP kinase inhibitor SB203580. Activation of exchange protein directly activated by cAMP (Epac) partially mimicked the effects of PACAP-38, and led to the phosphorylation of ERK but not p38 MAP kinase. These results provide evidence that the neurotrophic effects of PACAP-38 on human SH-SY5Y neuroblastoma cells are mediated by the PAC(1) receptor through a cAMP-dependent but PKA-independent mechanism, and furthermore suggest that this involves Epac-dependent activation of ERK as well as activation of the p38 MAP kinase signaling pathway.
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PMID:PACAP-38 induces neuronal differentiation of human SH-SY5Y neuroblastoma cells via cAMP-mediated activation of ERK and p38 MAP kinases. 1799 38

Burkholderia pseudomallei is the causative agent of melioidosis, and its infection usually affects patients' lungs. The organism is a facultative intracellular Gram-negative bacillus commonly found in soil and water in endemic tropical regions. Another closely related Burkholderia species found in soil and water is B. thailandensis. This bacterium is a non-pathogenic environmental saprophyte. B. pseudomallei is considerably more efficient than B. thailandensis in host cell invasion and adherence. A previous study by our group demonstrated that after successfully invading cells, there was no difference in the ability to survive and to replicate between both Burkholderia species in cultured A549 human lung epithelial cells. In this study, Human Affymetrix GeneChips were used to identify the difference in gene expression profiles of A549 cells after a 2-h exposure to B. pseudomallei and B. thailandensis. A total of 280 of 22,283 genes were expressed at higher levels in the B. pseudomallei-infected cells than in the B. thailandensis-infected cells, while 280 genes were expressed at lower levels in the B. pseudomallei-infected cells. Approximately 9% of these genes were involved in immune response and apoptosis. Those genes were further selected for gene expression analysis using reverse transcription PCR and/or real-time RT-PCR. The results of RT-PCR and real-time RT-PCR are in accordance with data from the microarray data in that bcl2 gene expression in the B. pseudomallei-infected cells was 2-fold higher than the level in the B. thailandensis-infected cells even though no apoptosis was seen in the infected cells. The levels of E-selectin, ICAM-1, IL-11, IRF-1, IL-6, IL-1beta and LIF genes expression in the B. pseudomallei-infected cells were 1.5-5 times lower than in the B. thailandensis-infected cells. However, both species stimulated the same level of IL-8 production from the tested epithelial cell line, and no difference in the ratio of adherent polymorphonuclear cells (PMNs) to infected A549 cells of both species was observed. Taken together, our results suggest that B. pseudomallei manipulates host response in favor of its survival in the host cell, which may explain the more virulent characteristics of B. pseudomallei when compared with B. thailandensis.
Asian Pac J Allergy Immunol 2009 Mar
PMID:Differential gene expression profiles of lung epithelial cells exposed to Burkholderia pseudomallei and Burkholderia thailandensis during the initial phase of infection. 1954 31


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