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

Bcl-2 is a key protein involved in the control of apoptosis. Our previous studies on breast and endometrium indicated hormonal regulation of bcl-2 in these tissues. In the present work we have analyzed Bcl-2 and Bax protein expressions in MCF-7 and T47-D, 2 hormone-dependent breast-cancer cell lines, by immunoblots. Estradiol markedly increased Bcl-2 protein content, both in short- and in long-term treatments of MCF-7 cells. Two types of anti-estrogens (4-hydroxytamoxifen and RU 58668) were able to reverse this effect. Also, a synthetic progestin (ORG 2058) was able to decrease the Bcl-2 level in T47-D cells. The level of Bax protein, however, was not affected in the same conditions of hormonal treatments. The level of Bcl-2 expression was 4.5-fold higher in MCF-7 than in MDA-MB 231 (an estradiol-independent cell line). From these results, we infer the existence of hormonal regulation of Bcl-2 expression and evoke a novel role for estradiol and progestin in the genesis of breast cancer.
Int J Cancer 1996 Sep 27
PMID:Antagonism between estradiol and progestin on Bcl-2 expression in breast-cancer cells. 889 51

To investigate the mechanism of oxidative stress induced death of PC12 cells, we performed confocal and flow cytometric analysis with a reactive oxygen species (ROS)-specific fluorogen, 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate, di(acetoxymethyl ester) (C-DCDHF-DA). Hydrogen peroxide significantly decreased the number of viable PC12 cells after 24 h. Hydrogen peroxide caused membrane blebbing, nuclear condensation and DNA fragmentation, indicating that the PC12 cells died due to apoptosis. The hydrogen peroxide-triggered apoptosis of PC12 cells was associated with enhanced ROS production in a dose-dependent manner by measuring with C-DCDHF-DA. Nerve growth factor (NGF) and Bcl-2 inhibited the hydrogen peroxide-induced apoptosis of PC12 cells. Neither of them, however, reduced the ROS production in PC12 cells. These data suggest that NGF or Bcl-2 protects PC12 cells from hydrogen peroxide-triggered apoptosis independently from ROS production.
J Biochem 1996 Sep
PMID:Free radical-independent protection by nerve growth factor and Bcl-2 of PC12 cells from hydrogen peroxide-triggered apoptosis. 890 18

Inactivation of resorbing osteoclasts by calcitonin is associated with typical morphological changes and alteration of the specific organization of osteoclast cytoskeleton. Here we show that calcitonin also promotes the survival of rat osteoclasts in vitro, cultured either on glass or bone, by delaying the onset of apoptosis. Parathyroid hormone had no effect on osteoclasts cultured on glass but it slightly increased apoptosis index of osteoclasts cultured on bone. Calcitonin was also able to rescue osteoclasts in calvarial explant cultures. The survival effect of calcitonin was mimicked by dibutyryl cAMP and could not be blocked by various metabolic inhibitors known to affect the apoptotic pathway. However, clodronate-induced apoptosis of osteoclasts could not be reversed by calcitonin and neither could calcitonin rescue osteoclasts already committed to apoptosis. It did not alter the distribution of Bcl-2 in osteoclasts. Our results show that at least in vitro calcitonin protects osteoclasts from apoptosis and suggest that it regulates the onset of apoptosis.
Mol Cell Endocrinol 1996 Sep 18
PMID:Calcitonin promotes osteoclast survival in vitro. 890 42

The human T lymphoma cell line Hut78 was transfected with Bel-2 gene or with control G418 Neomycin resistance-conferring plasmid. Bcl-2 transfected and Neomycin selected Hut78 cells expressed about ten-fold greater Bcl-2 protein than the neo-transfected controls. Susceptibility of Bcl-2-transfected Hut78 cells to human NK cells, human mixed lymphocyte reaction-generated cytotoxic effector cells, and mouse cytotoxic spleen cells generated by immunization with Hut78 cells was examined. In all systems tested, Bcl-2-transfected Hut78 target cells were significantly less susceptible to lysis than the neo-transfected control target cells. These results suggest that in Hut78 cells, Bcl-2 gene product may confer partial resistance to different types of cytotoxic effector mechanisms.
Immunol Lett 1996 Sep
PMID:Bcl-2 transfection protects Hut78 cell line from different types of cytotoxic effector cells. 890 2

In situ hybridization using EBERs and BHLF oligonucleotide probes and immunohistochemistry using monoclonal antibodies against LMP1, EBNA2, BZLF1 protein, p53 protein and bcl-2 protein were performed on 56 primary nasopharyngeal carcinomas. EBERs was detected in 46 cases (82%), and LMP in 17 cases (30%), but EBNA2 was not detected. While 30 of 32 cases (94%) in differentiated non-keratinizing carcinoma (NKC) and 16 of 17 cases (94%) in undifferentiated carcinoma (UNPC) showed EBERs, neither 5 cases of squamous cell carcinoma (SCC) nor 2 cases of adenocarcinoma showed EBERs. This finding confirms latent infection of EBV, especially phenotypical latency II, in NKC and UNPC but not in SCC. Bcl-2 protein was positive in 50 cases (89%), but its expression did not depend on expression of LMP1, which did not demonstrate induction of bcl-2 by LMP1 as seen in vitro. Cytoplasmic BZLF1 expression was detected in 18 cases (32%) whereas BHLF was positive only in 6 cases (11%). This suggests dysfunction of BZLF1, which disrupts viral latency despite its expression. p53 protein was positive in 31 cases (55%), and there was a distinct correlation between expression of BZLF1 and p53 protein (p < 0.001). This suggests that the interaction between BZLF1 protein and p53 protein, which inactivate each other, is one of the tumorigenic factors in NPC.
Rinsho Byori 1996 Sep
PMID:[Interaction between Epstein-Barr virus (EBV) gene expression and antibodies to EBV in nasopharyngeal carcinomas]. 891 Oct 67

Immature cerebellar granule neurons die by apoptosis within 1 week in vitro unless maintained in depolarizing (high) concentrations of potassium (25 mM K+). Neurons allowed to survive and differentiate in high K+ medium for several days in vitro are still induced to undergo apoptosis when switched back to physiological (low) concentrations of K+ (5 mM). Here we have investigated the effects of various cytokines and growth factors in these two well-defined paradigms of neuronal apoptosis. Tumour necrosis factor-alpha, leukaemia inhibitory factor, ciliary neurotrophic factor, interleukin-10 and interleukin-13 delayed apoptosis and prolonged survival of cerebellar granule neurons maintained in low K+ medium. The effect observed required continuous exposure of the cultures to the cytokines and appeared not to involve modulation of Bcl-2 protein expression. Brain-derived neurotrophic factor accelerated neuronal death in low K+ medium. In contrast, when apoptosis of the neurons was precipitated by switching mature high K+ neurons to low K+ medium, neither tumour necrosis factor-alpha, leukaemia inhibitory factor, ciliary neurotrophic factor, interleukin-10 nor interleukin-13 prevented apoptosis. When testing the cytokines and growth factors for their capacity to alter N-methyl-D-aspartate receptor-mediated excitotoxicity of differentiated cerebellar granule neurons, no significant effect was observed. These data appear to define a maturation-dependent modulation of cerebellar granule cell survival by cytokines and neurotrophic factors that are expressed in a developmental pattern in the mammalian brain.
Eur J Neurosci 1996 Sep
PMID:Maturation-dependent modulation of apoptosis in cultured cerebellar granule neurons by cytokines and neurotrophins. 892 Dec 90

Bcl-x is a Bcl-2-family protein that has been previously detected in cortical thymocytes, plasma cells, and activated lymphocytes. We report here on the high detection rate of the Bcl-x protein found in 86% of Hodgkin's disease samples and on the significance regarding its complex role among the Bcl-2-family of proteins: Bcl-x is known to heterodimerize with Bcl-2 (an anti-apoptosis protein) and with Bax, a potent inducer of cell death. Moreover, recent evidences show that Bcl-x may induce multiple drug resistance in vitro, suggesting that chemical or biological interactions with this protein may have potential therapeutic value in Hodgkin's disease.
Leuk Lymphoma 1996 Sep
PMID:Bcl-x gene expression in Hodgkin's disease. 902 97

In a number of experimental systems, the early stage of the apoptotic process, i.e., the stage that precedes nuclear disintegration, is characterized by the breakdown of the inner mitochondrial transmembrane potential (delta psi m). This delta psi m disruption is mediated by the opening of permeability transition (PT) pores and appears to be critical for the apoptotic cascade, since it is directly regulated by Bcl-2 and since mitochondria induced to undergo PT in vitro become capable of inducing nuclear chromatinolysis in a cell-free system of apoptosis. Here, we addressed the question of which apoptotic events are secondary to mitochondrial PT. We tested the effect of a specific inhibitor of PT, bongkrekic acid (BA), a ligand of the mitochondrial adenine nucleotide translocator, on a prototypic model of apoptosis glucocorticoid-induced thymocyte death. In addition to abolishing the apoptotic delta psi m disruption, BA prevents a number of phenomena linked to apoptosis: depletion of nonoxidized glutathione, generation of reactive oxygen species, translocation of NF kappa B, exposure of phosphatidylserine residues on the outer plasma membrane, cytoplasmic vacuolization, chromatin condensation, and oligonucleosomal DNA fragmentation. BA is also an efficient inhibitor of p53-dependent thymocyte apoptosis induced by DNA damage. These data suggest that a number of apoptotic phenomena are secondary to PT. In addition, we present data indicating that apoptotic delta psi m disruption is secondary to transcriptional events. These data connect the PT control point to the p53- and ICE/ Ced 3-regulated control points of apoptosis and place PT upstream of nuclear and plasma membrane features of PCD.
J Exp Med 1996 Sep 01
PMID:Mitochondrial permeability transition is a central coordinating event of apoptosis. 906 32

Splenic lymphoma with villous lymphocytes (SLVL) is a low grade lymphoproliferation characterized by a massive splenomegaly, an absence of lymphadenopathy and the presence in the peripheral blood of atypical B-lymphocytes with hairy-cell appearance. We have studied the morphological, immunological and molecular characteristics of 3 cases of SLVL. SLVL presented on blood smears characteristic irregularities of the plasma membrane consisting in thin and short villi unevenly distributed. The main phenotype was CD5-, CD11c+, and CD25-, but individual SLVL cases can not be identified by using immunohistochemical criteria alone. Clonal rearrangements of the immunoglobulin heavy chain gene were found in all 3 cases and in one case presented a bcl2-JH rearrangement. SLVL are clonal B-cell lymphoproliferations and can be associated with t(14; 18) translocation.
Ann Pathol 1996 Sep
PMID:[Splenic lymphoma with villous lymphocytes: morphologic, immunologic and molecular study. Report of three cases]. 917 20

B lymphocyte differentiation proceeds through a series of alternating stages of proliferative expansion interspersed with noncycling stationary phases during which cells undergo either positive selection or apoptotic cell death. The molecular control of cell cycle progression and that of apoptosis appear to be interconnected. Overexpression of Bcl-2 in lymphocytes or fibroblasts antagonizes apoptosis and delays their transition from the quiescent state into the cell cycle. We have undertaken a systematic analysis of the impact of bcl-2 transgene expression on cell cycle distribution and turnover rate of developing B lymphocytes in normal mice and in mutant animals in which B cell differentiation is arrested at the pro-B/pre-BI or the pre-BII stage. These experiments revealed that overexpression of Bcl-2 reduces proliferation and slows turnover of B cells at all stages of development. This demonstrates that Bcl-2 can retard transition of B cells between the quiescent and the cycling state regardless of the mitogenic stimulus and the differentiation stage. The implications of these results for the normal control of B lymphopoiesis and for lymphomagenesis are discussed.
J Immunol 1997 Sep 01
PMID:Expression of a bcl-2 transgene reduces proliferation and slows turnover of developing B lymphocytes in vivo. 927 19


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