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

We carried out a retrospective immunohistochemical study of Ki-67, PCNA, Bcl-2, BAX, BclX, and VEGF expression in tumors of two groups of breast cancer patients with favorable and unfavorable course of the disease. Considerably enhanced VEGF expression was detected in tumors of patients with early relapses of breast cancer. High VEGF expression was paralleled by high level of Ki-67 and PCNA expression in tumors. It can be hypothesized that expression of VEGF, Ki-67, and PCNA in primary tumor can be used for predicting the course of breast cancer or detecting the patients at a high risk of early relapses.
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PMID:Expression of biomolecular markers (Ki-67, PCNA, Bcl-2, BAX, BclX, VEGF) in breast tumors. 1527 70

Data are described on a retrospective immunohistochemical study of the Ki-67, PCNA, Bcl-2, BAX, BclX and VEGF expression in tumors of two groups of patients with breast cancer (BC) and with the favorable and unfavorable clinical courses. A reliably high level of VEGF expression was detected in tumors of patients with an early BC relapse. Apart from VEGF, higher levels of the Ki-67 and PCNA expression were registered in tumors of the discussed patient's category. It can be suggested that the expression parameters of VEGF, Ki-67 and PCNA in the primary tumor can be made use of in evaluating the BD prognostications or describing the features of high-risk groups with a high probability of early disease relapses.
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PMID:[The specificity of expression of molecular biological markers in tumors of the mammary gland]. 1532 May 47

Reports concerning the influence of exercise loading and steroid administration on dystrophinopathy are inconsistent. To investigate the effect of muscle exercise in Duchenne muscular dystrophy (DMD), 15 control and 15 mdx mice, an animal model of DMD, were divided into free-living (n = 6), exercise (n = 6), and immobilization (n = 3) groups. Free-living and exercise groups were further divided into steroid-treated and sham-treated groups to evaluate the effect of steroid administration. We measured apoptotic changes by in situ DNA nick-end labeling (TUNEL), DNA fragmentation assay, and Western blotting for Bcl-2 and BAX. Apoptosis was most prominent in the sham-treated exercise group, and it was significantly reduced in the steroid-treated exercise group. The steroid-treated free-living group showed a higher rate of apoptotic change than the sham-treated free-living group. Apoptosis was minimized in the free-living condition, whereas exercise loading and immobilization caused apoptotic change in this muscular dystrophy animal model. Steroid administration induced apoptosis in muscle of free-living mice, but alleviated the apoptotic damage caused by exercise loading in mdx mice. These findings suggest that steroid administration may be effective in preventing a postexercise deterioration of skeletal muscle in animal models of DMD.
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PMID:Effects of exercise and steroid on skeletal muscle apoptosis in the mdx mouse. 1537 34

Taurine is an abundant free amino acid that interacts with the potent oxidant hypochlorous acid to form the less toxic and more stable oxidant taurine monochloramine (TauNHCl). TauNHCl has diverse cellular effects ranging from inhibiting the production of proinflammatory mediators to inhibiting cell proliferation and inducing cell death. We hypothesized that TauNHCl could activate a cell death pathway involving Bcl-2 members and the activation of caspase proteases. FL5.12 cells are lymphocytic cells that undergo apoptosis following interleukin-3 (IL-3) withdrawal. Therefore, cell death following TauNHCl treatment of FL5.12 cells was compared and contrasted with IL-3 withdrawal. We found that TauNHCl treatment activates a cell death pathway with kinetics very similar to IL-3 withdrawal. TauNHCl-treated cells undergo an annexin V-positive/propidium iodide-negative phase of death consistent with apoptosis. TauNHCl treatment results in a conformational change in BAX that is associated with its activation. Both Bcl-2 and, to a lesser degree, the dominant negative form of caspase-9 inhibit cell death following TauNHCl treatment. In contrast with IL-3 withdrawal, TauNHCl treatment of FL5.12 cells results in a rapid cell cycle arrest that is cell cycle phase-independent. These results demonstrate that TauNHCl treatment induces a rapid, cell cycle-independent proliferative arrest followed by the activation of a cell death pathway involving Bcl-2 family members and caspase activation.
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PMID:Taurine monochloramine activates a cell death pathway involving Bax and Caspase-9. 1554 81

Bax is a pro-apoptotic member of the Bcl-2 family of proteins involved in the regulation of genetically programmed cell death in mammalian cells. It has been shown that heterologous expression of Bax in several yeast species, such as Saccharomyces cerevisiae, Schizosaccharomyces pombe and Pichia pastoris, also induces cell death. In this study we investigated the effects of Bax expression in the pathogenic yeast Candida albicans. Cell death inducing expression of Bax required a synthetic BAX gene that was codon-optimized for expression in Candida albicans. Expression of this BAX gene resulted in growth inhibition and cell death. By fusing Bax with the yeast enhanced green fluorescent protein of Aequoria victoria, the cell death-inducing effect of Bax was increased due to reduced proteolytic degradation of Bax. Using this fusion protein we showed that, upon expression in C. albicans, Bax co-localizes with the mitochondria. Furthermore, we showed for the first time that expression of Bax in yeast causes the mitochondria, which are normally distributed throughout the cell, to cluster in the perinuclear region.
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PMID:Bax-induced cell death in Candida albicans. 1556 45

Bak is generally recognized as a multidomain, pro-apoptotic member of the Bcl-2 family. Bak and Bax are functionally redundant in non-neuronal cells and represent a mitochondrial convergence point for cell death signaling pathways. This functional redundancy, however, may not exist in neurons in which the single deletion of Bax is sufficient to confer protection against a variety of cytotoxic insults. In the present study, we demonstrate that postnatal cortical and cerebellar granule neurons exclusively express an alternatively spliced, BH3 domain-only form of Bak (N-Bak), whereas astrocytes express only the full-length, multidomain form. Overexpression of N-Bak promotes Bax translocation in HeLa cells and induces neuronal cell death in cortical, hippocampal, and cerebellar granule neurons in a Bax-dependent manner. N-Bak interacts with Bcl-XL but not BAX, suggesting an indirect mechanism for promoting Bax translocation to the mitochondria. N-Bak message and protein levels are elevated in cortical neurons in response to DNA damage, and subsequent induction of neuronal death is significantly delayed by expressing a full-length Bak antisense plasmid. These results demonstrate that postnatal neurons solely express a BH3 domain-only form of Bak, which contributes to DNA damage-induced neuronal apoptosis. The absence of full-length Bak expression explains the near exclusive requirement for Bax in neuronal apoptosis.
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PMID:Neurons exclusively express N-Bak, a BH3 domain-only Bak isoform that promotes neuronal apoptosis. 1559 Jun 65

A time course study was performed to reveal the sequence of histopathology after Trichinella spiralis or T. pseudospiralis infection in mice. A cyst was formed in the former case by about 18 days post infection and prominent myopathy was restricted within the cyst. In the latter case, however, no typical cyst was formed, and myopathy spread diffusely over the infected muscle tissues occupying half the area of muscle sections. An electron microscope observation revealed that the disintegration of muscle cells was delayed in T. pseudospiralis infection than in T. spiralis infection. Quantitative reverse transcription polymerase chain reaction (RT-PCR) showed that apoptosis-related genes were expressed for a longer term in muscles infected with T. pseudospiralis than in those with T. spiralis, although the same spectrum of genes are mobilized. Examined apoptosis-related genes included tumor suppressor genes p53, p53; mouse double minute 2, MDM2; cyclin-dependent kinase inhibitor p21 (WAF1), p21(waf) ; Bcl-2 associated protein X, BAX; apoptotic protease activating factor 1, Apaf-1; Caspase 9 and serine/ threonine protein kinase, PKB. Micro-dissection of the infected muscle tissue and subsequent RT-PCR confirmed that the expressions of these genes are restricted to tissue with myopathy. Thus, the expression of the apoptosis-related genes correlated with continuous and diffuse myopathy caused by T. pseudospiralis infection.
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PMID:Trichinella pseudospiralis infection is characterized by more continuous and diffuse myopathy than T. spiralis infection. 1594 11

Garcinol, from the fruit rind of Garcinia indica and other species, has been reported to suppress colonic aberrant crypt foci (ACF) formation in rats. In this study, we investigate the beneficial effects of tumor prevention by garcinol on the human colorectal cancer cell line, HT-29. Focal adhesion kinase (FAK) is the major signaling mediator of integrin-mediated cell-matrix contact-regulated cellular proliferation, migration, and apoptosis in adherent cells. Results of Matrigel analysis show that exposure of HT-29 cells to 10 microM garcinol inhibited cell invasion, and decreased the dose-dependent tyrosine phosphorylation of FAK. We further demonstrate by Western blot analysis that garcinol inhibited activation of the Src, MAPK/ERK, and PI3K/Akt signaling pathways. To investigate whether the loss of integrin-mediated cell-matrix contact can induce apoptosis, we demonstrate that garcinol induced it in HT-29 cells. The apoptotic dose of garcinol (20 microM) changed the ratio of the anti-apoptotic Bcl-2 and proapoptotic BAX proteins within 12 h, which correlated with a release of cytochrome c from the mitochondria to the cytosol, and with PARP cleavage. Additionally, we demonstrate that a decreasing MMP-7 protein level in HT-29 cells results in sensitization to garcinol. Garcinol also significantly inhibited the expression of MMP-7 in IL-1beta-induced HT-29 cells. These results suggest that garcinol reduces cell invasion and survival through the inhibition of FAK's downstream signaling.
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PMID:Garcinol modulates tyrosine phosphorylation of FAK and subsequently induces apoptosis through down-regulation of Src, ERK, and Akt survival signaling in human colon cancer cells. 1605 81

Gastrointestinal neuroendocrine tumours (NET) represent a heterogeneous tumour entity. The anti-neoplastic therapy of advanced NET disease is still unsatisfactory and innovative therapeutic approaches are needed. As NET frequently express insulin-like growth factors (IGFs) and their receptors (IGFR), known to promote survival, oncogenic transformation, tumour growth and spreading, the inhibition of the IGF/IGF-receptor system may offer possibilities for novel targeted treatment strategies of NET. Here, we studied the anti-neoplastic effects of an inhibition of the IGF-I receptor (IGF-1R) signalling in NET cells by the novel IGF-1R tyrosine kinase (TK) inhibitor NVP-AEW541, whose anti-neoplastic potency has not yet been tested in NET disease. Using two human NET cell lines with different growth characteristics, we demonstrated that NVP-AEW541 dose-dependently inhibited the proliferation of NET cells by inducing apoptosis and cell cycle arrest. Anti-neoplastic effects of NVP-AEW541 were also detected in primary cultures of human neuroendocrine gastrointestinal tumours. Apoptosis was characterized by activation of the apoptotic key enzyme, caspase-3, as well as by detection of changes in the expression of the pro- and anti-apoptotic proteins, BAX and Bcl-2, after NVP-AEW541 treatment. Cell cycle was arrested at the G1/S checkpoint. The anti-neoplastic effects of NVP-AEW541 involved the inactivation of ERK1/2. Induction of immediate cytotoxicity did not account for the anti-neoplastic effects of NVP-AEW541, as shown by measurement of lactate dehydrogenase release. Moreover, additive anti-neoplastic effects were observed when NVP-AEW541 was combined with cytostatics such as doxorubicin or the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin. This is the first report on the induction of apoptosis and cell cycle arrest by the IGF-1R-TK inhibitor, NVP-AEW541, in NET cells. The inhibition of the IGF/IGFR system appears to be a promising novel approach for future treatment strategies of NET disease.
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PMID:The insulin-like growth factor receptor 1 is a promising target for novel treatment approaches in neuroendocrine gastrointestinal tumours. 1660 Dec 84

PUMA is a BH3-only Bcl-2 family protein that plays an essential role in DNA damage-induced apoptosis. PUMA interacts with anti-apoptotic Bcl-2 and Bcl-X(L) and is dependent on Bax to induce apoptosis. In this study, we investigated how the interactions of PUMA with the antiapoptotic proteins coordinate with Bax to initiate apoptosis in HCT116 colon cancer cells. We found that Bcl-X(L) was most effective among several antiapoptotic proteins in suppressing PUMA-induced apoptosis and PUMA-dependent apoptosis induced by the DNA-damaging agent adriamycin. Mutant Bcl-X(L) that cannot interact with Bax was unable to protect cells from PUMA-mediated apoptosis. Knockdown of Bcl-X(L) by RNA interference significantly enhanced PUMA-mediated apoptosis in HCT116 cells but not in PUMA-knockout cells. Furthermore, Bax was found to be dissociated preferentially from Bcl-X(L) in HCT116 cells but not in the PUMA-knockout cells, in response to PUMA induction and adriamycin treatment. PUMA inhibited the association of Bax and Bcl-X(L) in vitro by directly binding to Bcl-X(L) through its BH3 domain. Finally, we found that wild-type Bax, but not mutant Bax deficient in either multimerization or mitochondrial localization, was able to restore PUMA-induced apoptosis in the BAX-knockout cells. Together, these results indicate that PUMA initiates apoptosis in part by dissociating Bax and Bcl-X(L), thereby promoting Bax multimerization and mitochondrial translocation.
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PMID:PUMA Dissociates Bax and Bcl-X(L) to induce apoptosis in colon cancer cells. 1660 47


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