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)

As a first step towards elucidating the potential role(s) of bcl-2 and bcl-2-related genes in lung tumorigenesis and therapeutic responsiveness, the expression of these genes has been examined in a panel of lung cancer cell lines derived from untreated and treated patients, and in cell lines selected in vitro for multidrug resistance. Bcl-2 was hyperexpressed in 15 of 16 small-cell lung cancer (SCLC) cell lines and two of five non-small-cell lung cancer (NSCLC) lines compared with normal lung and brain, and hyperexpression was not chemotherapy related. Bcl-x was hyperexpressed in the majority of SCLC and NSCLC cell lines as compared with normal tissues, and all lung tumour lines preferentially expressed bcl-x1-mRNA, the splice variant form that inhibits apoptosis. Bax gene transcripts were hyperexpressed in most SCLC and NSCLC cell lines examined compared with normal adult tissues. Mutant p53 gene expression was detected in the majority of the cell lines and no relationship between p53 gene expression and the expression of either bcl-2, bcl-x or bax was observed. No changes in bcl-2, bcl-x and bax gene expression were observed in multidrug-resistant cell lines compared with their drug-sensitive counterparts.
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PMID:Expression of apoptosis-regulatory genes in lung tumour cell lines: relationship to p53 expression and relevance to acquired drug resistance. 863 Feb 78

Baxalpha was isolated due to its interaction with Bcl-2. Baxalpha overexpression in an interleukin (IL)-3 dependent cell line accelerates apoptosis upon removal of the cytokine. The ratio of Baxalpha to Bcl-2 appears to be crucial for the effect. To study the action of the bax gene product in vivo, we have generated transgenic mice overexpressing Baxalpha specifically in T cells. Such T cells show accelerated apoptosis in response to gamma-radiation, dexamethasone and etoposide. By crossing baxalpha mice with bcl-2 transgenics we show that the critical nature of the Baxalpha:Bcl-2 ratio holds in primary T cells and that it can be manipulated to elicit a strong response to previously resisted stimuli. p53 has a role in the regulation of apoptosis in response to DNA-damaging agents. p53 directly activates transcription of the bax gene. The presence of the baxalpha transgene accelerated apoptosis in thymocytes from both p53-l- and p53+l- mice in response to dexamethasone. Thymocytes from p53-l- mice with the baxalpha transgene showed similar resistance to apoptosis by DNA-damaging agents as did p53-l- mice without the transgene. Baxalpha overexpression alone cannot restore the DNA damage apoptosis pathway, suggesting that p53 is required to induce or activate other factor(s) to reconstitute the response fully.
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PMID:T cells from baxalpha transgenic mice show accelerated apoptosis in response to stimuli but do not show restored DNA damage-induced cell death in the absence of p53. 863 54

Bcl-2 expression is able to confer drug resistance to chemotherapy-induced programmed cell death. Bax, a partner protein of bcl-2 with extensive aminoacid homology, is a promoter of apoptosis. Apparently the equilibrium of bcl-2 and bax hetero- and homodimers is important for the susceptibility of cells for stimuli inducing apoptosis. In this study we determined the role of bcl-2 to bax expression ratio, bcl-xL and ICE expression level for predicting clinical response to chemotherapy in acute myelold leukemia (AML). Bone marrow samples from 14 patients with AML were examined using an immunophosphatase staining method. Initial bone marrow blast portion was over 80% in all cases. Clinical response was defined by bone marrow aspiration 4 weeks after treatment initiation. There was a significant correlation between bcl-2 to bax expression ratio and clinical response (P < 0.005). No patients with a bcl-2/bax ratio >1.0 achieved complete remission after induction therapy. No significant correlation between bcl-2- and p-glycoprotein-expression was observed in this group. Conversely a high expression of ICE indicated a good clinical response (P < 0.01), whereas expression of bcl-xL had no influence on therapeutic success in this group.
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PMID:Association of bcl-2, bax, bcl-xL and interleukin-1 beta-converting enzyme expression with initial response to chemotherapy in acute myeloid leukemia. 865 95

The expression of apoptosis-regulating proteins, Bcl-2, Bax, Mcl-1, and Bcl-X, was evaluated by immunohistochemical methods in 39 cases of thyroid carcinomas. Normal thyroid tissues showed a consistent expression of Bcl-2 and Mcl-1 whereas Bax and Bcl-X proteins were essentially absent from most follicular thyroid cells. Bax expression was observed in all papillary carcinomas (n = 23) and in 8 of 10 follicular carcinomas. The intensity of Bcl-2 immunostaining was generally higher in follicular tumors (n = 10) than in papillary carcinomas (n = 21 of 23). However, in undifferentiated tumors, both Bax and Bcl-2 were weakly expressed. Mcl-1 protein expression was similar to that of Bax in papillary and follicular tumors, but was also frequently detectable in undifferentiated tumors. Bcl-X immunostaining was seen in all undifferentiated tumors (n = 6), in 22 of 23 papillary tumors, and in 5 of 10 follicular tumors. Our findings show that the regulation of bcl-2 family gene expression is different in normal thyroid tissue compared to that of its neoplastic counterpart and varies with the tumor subtype. In particular, unlike normal thyroid epithelium, the apoptosis-blocking gene bcl-X and the apoptosis-inducing gene bax are frequently expressed in thyroid carcinomas derived from the follicular cells. Thus, alterations in the expression of these bcl-2 family genes may contribute to the pathogenesis of thyroid carcinomas.
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PMID:Expression of the cell death-inducing gene bax in carcinomas developed from the follicular cells of the thyroid gland. 867 2

Deregulation of bcl-2 may function as a survival mechanism in cancer cells, predisposed to cell death. Aberrant Bcl-2 expression is a frequent occurrence in chronic atrophic gastritis, gastric epithelial dysplasia and gastric cancer. Inhibition of apoptosis through Bcl-2 expression appears to be specifically associated with promotion of gastric adenocarcinoma. In addition, loss of heterozygosity of the bcl-2 gene is a common event in well-differentiated adenocarcinoma, whereas overexpression of bcl-2 gene is observed in poorly differentiated adenocarcinoma. Bax, a homologue of Bcl-2, counters the death repressor activity of Bcl-2. In our study Bax immunostaining in gastric cancer tissue is not significantly correlated with tumor histology. Possible gene therapy using bax gene is discussed.
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PMID:[Expression of Bcl-2 and Bax in human gastric cancer tissue]. 874 90

During early pregnancy, the uterine endometrium responds to an implanting blastocyst with the extensive growth and differentiation of decidualization. This transformation of endometrial stromal cells begins in the antimesometrial side of the uterus to form a primary decidual zone, expands to form a secondary zone in the antimesometrium, and eventually transforms stromal cells in the mesometrial region. During pregnancy, both decidual zones regress by apoptosis, leaving decidual cells in the mesometrial region to form decidua basalis and the mature placenta. Molecular mechanisms controlling cell death during blastocyst implantation and decidualization are unknown. We examined the hypothesis that progesterone and estrogen control of endometrial differentiation and eventual apoptosis involves control of bcl-2 gene family expression. Ovariectomized rats were primed with estradiol and treated with progestin (medroxyprogesterone acetate, 3.5 mg) and estradiol (200 ng) before an intrauterine stimulus to initiate decidualization. Expression of the two bax messenger RNA transcripts, 1.0 and 1.5 kilobases, was examined by Northern blot analysis after hormone treatment and decidualization, and only the 1.0-kilobase transcript was induced. After the same treatments, the expression of bcl-2, a suppressor of apoptosis, decreased. In situ analysis revealed a cell type-specific increase in bax expression after the hormonal treatment and decidualization. This increase was first seen in luminal and glandular epithelial cells and then in the periluminal stroma 24 h after intrauterine stimulation, with eventual progressive expression throughout the stroma. Expression of bcl-2 decreased after hormone treatment and decidualization. Immunohistochemical studies of Bax showed that expression of Bax protein accompanied decidualization of the stroma. Bcl-2 protein was only seen in the luminal and glandular epithelia, and its level decreased as decidualization progressed. These data indicate that the balance between bax and bcl-2 expression is altered during stromal cell differentiation. Increased expression of bax precedes nucleosomal DNA fragmentation and eventual apoptosis, which plays a significant role in placental development.
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PMID:Effect of decidualization on the expression of bax and bcl-2 in the rat uterine endometrium. 877 Sep 38

The proto-oncogene c-myc has been implicated in both cellular proliferation and apoptosis, and we have shown that overexpression of c-myc can induce polycystic kidney disease in transgenic mice. To elucidate the molecular and cellular defects underlying cystogenesis, we have investigated the potential roles of cell proliferation and apoptosis as they relate to c-myc and modulators of c-myc function in human autosomal dominant polycystic kidney disease (ADPKD). Renal c-myc expression was consistently elevated, up to 15-fold, in ADPKD. High levels of c-myc expression correlated with 10- to 100-fold increased proliferation index in cystic epithelium. Interestingly, steady-state levels of bcl-2 mRNA were also increased up to 20-fold and Bcl-2 protein was markedly elevated. In contrast, the expression of bax and p53 was virtually unchanged. However, apoptosis was consistently and significantly increased in ADPKD kidneys, unchecked by high levels of Bcl-2. Together with proliferation, apoptosis may thus represent a general mechanism for cyst growth and tissue remodeling. We conclude that both epithelial cell proliferation and apoptosis required for normal kidney homeostasis are deregulated in ADPKD, recapitulating the renal developmental program. Furthermore, abnormal expression of proto-oncogenes regulating these processes is an important mediator of cystogenesis in human ADPKD.
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PMID:Dysregulation of cellular proliferation and apoptosis mediates human autosomal dominant polycystic kidney disease (ADPKD). 880 89

The proto-oncogene bcl-2 and its family members, bcl-x and bax are recognized as major regulators of cell death and survival. Although Bcl-2 and Bcl-x are expressed in brain, little is known how they are regulated in neurons. Here we have studied the expression of bcl-2, bcl-xL and bax mRNA in rat cerebellar granule neurons cultured under conditions which influence neuron survival. Insulin-like growth factor-1 and brain-derived neurotrophic factor supported the survival of these neurons, but affected neither the expression of bcl-2, bcl-xL nor bax mRNA. In contrast, bcl-2 and bcl-xL mRNAs were up-regulated in cerebellar granule neurons plated at high density exhibiting an increased neuronal survival. Western blots showed that cell density also increased Bcl-2 protein level. However, conditioned medium from dense cultures did not affect the level of bcl-2 mRNA nor survival of the neurons. This suggests that cell density promotes survival and regulates Bcl-2 expression in cerebellar granule neurons through a signaling pathway different from known neurotrophic factors.
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PMID:Cell density increases Bcl-2 and Bcl-x expression in addition to survival of cultured cerebellar granule neurons. 880 10

The cooked meat mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) produces tumors at multiple sites in the F344 rat, including adenocarcinomas of the colon. In the present study, the development of IQ-induced colorectal tumors was shown to be accompanied by the progressive inhibition of programmed cell death. This was associated with increased expression of the antiapoptosis protein Bcl-2 and decreased expression of bax, a known activator of apoptosis. Carcinomas bearing high levels of bcl-2 expression exhibited low levels of p53, the tumor suppressor protein that in some circumstances has been shown to down-regulate bcl-2. Because they lack mutations in the genes commonly associated with increased cell proliferation (APC, Ki-ras, and p53) and show no evidence of microsatellite instability, IQ-induced colon tumors might arise via the deregulation of bcl-2 expression, leading to inhibition of programmed cell death.
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PMID:Inhibition of apoptosis in colon tumors induced in the rat by 2-amino-3-methylimidazo[4,5-f]quinoline. 881 12

Permanent occlusion of the middle cerebral artery in rats was used to assess the effects of focal ischemia on the expression of members of the bcl-2 family which have been implicated in the regulation of programmed cell death. Intraluminal occlusion of one middle cerebral artery for 6 h resulted in histologically detectable brain damage within the ipsilateral caudate putamen, basolateral cortex and parts of the thalamus. In the infarcted basolateral cortex and thalamus fragmentation of DNA was detected in many nuclei using in-situ end-labeling of DNA breaks by terminal transferase, whereas only scattered labeled nuclei were visible in the infarcted caudate putamen. Immunohistochemical analysis revealed activation of c-Fos in the infarcted cortex and thalamus and in the non-infarcted cingulate cortex as has been shown by others. A decrease in immunoreactivity for Bcl-2, and Bcl-X and an increase in immunostaining for Bax was observed exclusively in neurons within the ischemic cortex and thalamus. Within the infarcted caudate putamen, however, protein levels of all bcl-2 family members declined and c-Fos remained absent. By reverse transcription and polymerase chain reaction it was demonstrated that levels of bcl-2 mRNA markedly decreased in the ipsilateral hemisphere, whereas the amount of bax mRNA was elevated. These findings suggest that a shift in the ratio of cell death repressor Bcl-2 to cell death effector Bax and a concomitant activation of c-Fos may contribute to neuronal apoptosis in the infarcted thalamus and cortex.
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PMID:Altered expression of Bcl-2, Bcl-X, Bax, and c-Fos colocalizes with DNA fragmentation and ischemic cell damage following middle cerebral artery occlusion in rats. 887 9


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