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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 and p53 gene products (Bcl-2, p53) are important regulators of apoptosis and cell proliferation, and their immunohistochemical expression may help to identify high-risk breast cancer patients. The authors evaluated p53 and Bcl-2 immunoreactivity in 178 node-negative breast cancers (NNBC) with long-term follow-up (median, 60 months). Bcl-2 was seen in 111 (62%) cases, and was significantly associated with small tumor size, nonductal morphology, low tumor grade, estrogen-receptor (ER) positivity, and p53 negativity. p53 overexpression (ie, > 15% reactive nuclei) was observed in 31 (17%) cases, and was associated with lower age, large tumor size, ductal morphology, high tumor grade, negative ER status, and lack of Bcl-2 immunoreactivity. In univariate analysis, the variables associated with short relapse-free survival (RFS) were large tumor size (P = .002), high histological grade (P = .01), high mitotic count (P = .03), and high Nottingham prognostic index (NPI) (P = .0002). In multivariate analysis (final model), only the NPI was of independent prognostic value concerning RFS.
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PMID:Bcl-2 and p53 expression in node-negative breast carcinoma: a study with long-term follow-up. 891 23

This study investigates the extent of apoptosis in 53 testicular and ovarian germ cell tumors by using the in situ 3'-end DNA labeling technique on tumor sections. The tumors were also immunostained with antibodies to the p53 and bcl-2 proteins. The extent of apoptosis was highest in embryonal carcinoma (mean, 2.9%) followed by seminoma (mean, 1.1%), choriocarcinoma (mean, 0.7%) and immature teratoma (mean, 0.7%). In individual components of the mixed germ cell tumors the apoptotic index was in the same range as in the corresponding pure germ cell tumors. Mature teratomas rarely contained any apoptotic cells. Sixty-two percent of all the tumors expressed p53 protein. p53 expression was quantitatively strongest in embryonal carcinomas which also showed the highest level of apoptosis. Bcl-2 positivity could only be detected in some mesenchymal and epithelial components of the immature and mature teratomas; embryonal carcinomas, seminomas, or choriocarcinomas did not express bcl-2 at all. Our results show that the level of apoptosis in germ cell tumors associates with the histological type of the neoplastic component independent of whether it is singly present or a component of a mixed germ cell tumor. The results suggest that the quantity of p53 expression may contribute to the level of apoptosis in different tumor groups.
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PMID:Extent of apoptosis in relation to p53 and bcl-2 expression in germ cell tumors. 891 34

Apoptosis or programmed cell death represents a mechanism by which tumor cells with DNA damage can be deleted. Bcl-2 and p53 gene products have both been linked to apoptosis. Bcl-2 plays a role as an inhibitor of apoptosis that may extend the viability of cells containing genetic alterations and facilitate tumor progression. Mutant p53 has a similar effect. The purpose of this study was to investigate the relationship between bcl-2 and p53 expression and to clarify their roles in apoptosis in different histological graded breast carcinomas. We analysed 101 invasive ductal carcinomas of the breast for the expression of bcl-2, p53, c-erbB-2, estrogen and progesterone receptors using immunohistochemistry. Reciprocal expression of bcl-2 and p53 was present in 71.3% of cases. The bcl-2+/p53-expression pattern was prevalent in histological grade I and II tumors (77.4% and 59.3% respectively) and rarely present in histological grade III (6.3%). Conversely, bcl-2-/p53+ expression pattern was rarely present in histological grade I and II tumors (3.2% and 11.1% respectively) and prevalent in histological grade III (50.0%). Our results also showed that Bcl-2 expression was positively correlated with ER and PR, more prevalent in pre-menopausal status, and negatively correlated with cerbB-2 expression. Bcl-2 expression was involved in tumor progression in well-differentiated tumors and mutant p53 could substitute for bcl-2 function in poorly differentiated tumors. The bcl-2/p53 expression pattern of tumors may be of value in predicting therapeutic response and prognosis. Bcl-2 expression was correlated with other well-established prognostic factors and bcl-2 could be an estrogen-related protein.
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PMID:Reciprocal expression of Bcl-2 and p53 in breast ductal carcinoma. 891 21

Bcl-2 was first identified as a novel transcript associated with the t(14;18) chromosomal breakpoint which occurs in most follicular lymphomas. The deregulated expression of bcl-2 was found to contribute to multistep neoplasia through the suppression of cell death, or apoptosis, in transgenic mouse models. Bcl-2 was subsequently shown to be normally expressed in a variety of tissues and to significantly inhibit the induction of apoptosis in many experimental systems. Bcl-2 is now known to be structurally similar to other proteins, in particular within the domains referred to as BH1 and BH2. This multigene family of cell death regulators includes members which enhance rates of apoptosis, including bcl-xs and bax, and those which inhibit apoptosis, including MCL-1 and bcl-xL. Members of the bcl-2 family physically interact with other proteins, including other family members and these interactions appear to modulate their function. The mechanism(s) by which bcl-2 family members regulate cell death remain in large part unknown, although recent evidence suggests that bcl-2 may interfere with cellular signalling events involved in apoptosis induction.
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PMID:Importance of the Bcl-2 family in cell death regulation. 891 32

Immunohistochemical analysis of Bcl-2 oncoprotein, one of the oncogenes associated with the regulation of programmed cell death, was performed on 12 surgically resected tumors of the combined type of small-cell lung cancer. Ten cases (83%) expressed Bcl-2 oncoprotein within the tumor tissues. Two of them showed its expression in both the small cell carcinoma and non-small cell carcinoma types, and 7 cases exhibited Bcl-2 expression only in the portion of the small cell carcinoma. Considering previous reports indicating a high prevalence of Bcl-2 oncoprotein expression in small cell lung cancer, it is suggested that Bcl-2 oncoprotein even in the combined type of lung cancer may play an important role in tumorigenesis and tumor development and ensuing histological alterations between small cell carcinoma and non-small cell carcinoma types.
Tumour Biol 1996
PMID:Bcl-2 oncoprotein expression is increased especially in the portion of small cell carcinoma within the combined type of small cell lung cancer. 893 49

The prognosis of children with neuroblastoma (NB) is dependent upon the patient's age at diagnosis, the location of the primary tumor, and histologic tumor cell differentiation. These characteristics, as well as the presumption that NB results from clonal expansion of primitive cells involved in sympathetic nervous system (SNS) development, predict that a model of tumorigenesis based upon normal fetal SNS histogenesis might indicate tumor progenitor status and define biologic and clinical behavior. Immunohistochemistry and in situ hybridization were used to examine a panel of marker gene products predicted or shown to be expressed during SNS development in the normal human fetal SNS from 8 to 24 weeks' gestational age. A similar analysis was performed in a selection of clinical NB tumors, and the results were compared. In a subset of differentiating, often extra-adrenal NB tumors in patients who frequently had a favorable outcome; advancing morphologic tumor cell differentiation spatially paralleled an advancing fetal extra-adrenal chromaffin marker gene expression phenotype (ie, increasing TrkA, TrkC, TH, IGF-2, and neuron-specific enolase expression but a lack of phenylethanolamine N-methyltransferase expression). In these tumors, expression of gene products associated with normal fetal sympathetic ganglionic differentiation (ie, Bcl-2, HNK-1, and neuropeptide Y) was lost with morphologic tumor cell differentiation. In contrast, undifferentiated tumors, the majority of which were high stage, adrenal in origin, and prognostically unfavorable, displayed marker expression characteristics mirroring that of an early fetal ganglionic lineage. Thus, we show that morphologic differentiation in stroma-poor NB tumors, long held as an important prognostic feature in tumor grading systems, often corresponds to an extra-adrenal chromaffin rather than a ganglion cell or adrenal medullary chromaffin phenotype. Understanding the biology of extra-adrenal chromaffin tissues may provide an explanation for the clinically less aggressive nature of differentiating NB tumors and suggest potential mechanisms for spontaneous regression and/or treatment response.
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PMID:A developmental model of neuroblastoma: differentiating stroma-poor tumors' progress along an extra-adrenal chromaffin lineage. 894 Dec 12

Curcumin, widely used as a spice and coloring agent in food, possesses potent antioxidant, anti-inflammatory and anti-tumor promoting activities. In the present study, curcumin was found to induce apoptotic cell death in promyelocytic leukemia HL-60 cells at concentrations as low as 3.5 micrograms/ml. The apoptosis-inducing activity of curcumin appeared in a dose- and time-dependent manner. Flow cytometric analysis showed that the hypodiploid DNA peak of propidium iodide-stained nuclei appeared at 4 h after 7 micrograms/ml curcumin treatment. The apoptosis-inducing activity of curcumin was not affected by cycloheximide, actinomycin D, EGTA, W7 (calmodulin inhibitor), sodium orthovanadate, or genistein. By contrast, an endonuclease inhibitor ZnSO4 and proteinase inhibitor N-tosyl-L-lysine chloro-methyl ketone (TLCK) could markedly abrogate apoptosis induced by curcumin, whereas 12-O-tetradecanoylphorbol-13-acetate (TPA) had a partial effect. The antioxidants, N-acetyl-L-cysteine (NAC), L-ascorbic acid, alpha-tocopherol, catalase and superoxide dismutase, all effectively prevented curcumin-induced apoptosis. This result suggested that curcumin-induced cell death was mediated by reactive oxygen species. Immunoblot analysis showed that the level of the antiapoptotic protein Bcl-2 was decreased to 30% after 6 h treatment with curcumin, and was subsequently reduced to 20% by a further 6 h treatment. Furthermore, overexpression of bcl-2 in HL-60 cells resulted in a delay of curcumin-treated cells entering into apoptosis, suggesting that bcl-2 plays a crucial role in the early stage of curcumin-triggered apoptotic cell death.
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PMID:Curcumin, an antioxidant and anti-tumor promoter, induces apoptosis in human leukemia cells. 895 Jan 93

Cytokine-mediated cell death in tumor cells can be achieved through endogenous nitric oxide (NO) from within tumor cells or exogenous NO from either activated macrophages or endothelial cells. The purpose of this study was to determine the role of Bcl-2 in NO-mediated apoptosis. The incubation of murine L929 and NIH3T3 cells with interleukin-1 alpha (IL-1 alpha) and interferon gamma (IFN gamma) induced high endogenous NO production only in the L929 cells that also underwent apoptosis. NIH3T3 cells were not resistant to NO-mediated apoptosis. In fact, the incubation of L929 and NIH3T3 cells with exogenous NO derived from NO donors, sodium nitroprusside, or S-nitroso-N-acetyl-DL-penicillamine (SNAP) induced death, characterized by typical apoptotic morphology and DNA fragmentation, in both cell types, but to a higher degree in NIH3T3 cells than in the L929 cells. We then measured the effect of Bcl-2 expression on exogenous NO-induced apoptosis. At both the mRNA and protein levels, L929 fibroblasts expressed higher levels of endogenous mouse Bcl-2 than did NIH3T3 cells. At the same time, L929 cells were much more resistant to exogenous NO-induced cell death than were NIH3T3 cells. The inverse correlation between mouse Bcl-2 expression and sensitivity to exogenous NO-mediated cell death was also found in the murine K-1735 melanoma C-23 and X-21 clonal populations. Transfection of both NIH3T3 cells and L929 cells with the human bcl-2 gene led to resistance to both exogenous and endogenous NO-mediated apoptosis. These data demonstrate that NO-mediated apoptosis can be suppressed by expression of Bcl-2, suggesting that abnormal expression of Bcl-2 may influence the efficacy of tumor immunotherapy.
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PMID:Bcl-2 protects cells from cytokine-induced nitric-oxide-dependent apoptosis. 895 45

A number of apoptosis-inducing agents used in cancer therapy (etoposide, doxorubicin, 1-beta-D-arabinofuranosylcytosine), as well as the proapoptotic second messenger ceramide, induce a disruption of the mitochondrial transmembrane potential (delta psi m) that precedes nuclear DNA fragmentation. This effect has been observed in tumor cell lines of T-lymphoid, B-lymphoid, and myelomonocytic origin in vitro. Circulating tumor cells from patients receiving chemotherapy in vivo also demonstrate a delta psi m disruption after in vitro culture that precedes nuclear apoptosis. Transfection-enforced hyperexpression of the proto-oncogenes bcl-2 and bcl-XL protects against chemotherapy-induced apoptosis, at both the level of the mitochondrial dysfunction preceding nuclear apoptosis and the level of late nuclear apoptotic events. Bcl-2-mediated inhibition of ceramide-induced delta psi m disruption is observed in normal as well as anucleate cells, indicating that bcl-2 acts on an extranuclear pathway of apoptosis. In contrast to Bcl-2 and Bcl-XL, hyperexpression of the protease inhibitor cytokine response modifier A fails to protect tumor cells against chemotherapy-induced delta psi m disruption and apoptosis, although cytokine response modifier A does prevent the delta psi m collapse and posterior nuclear apoptosis triggered by cross-linking of Fas/Apo-1/CD95. In conclusion, delta psi m disruption seems to be an obligatory step of early (pre-nuclear) apoptosis, and delta psi m is stabilized by two members of the bcl-2 gene family conferring resistance to chemotherapy.
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PMID:Bcl-2 and Bcl-XL antagonize the mitochondrial dysfunction preceding nuclear apoptosis induced by chemotherapeutic agents. 898 42

Uterine leiomyoma is the most common benign smooth muscle cell tumor of the myometrium. Although Bcl-2 protein is known to be an apoptosis-inhibiting gene product and to prevent apoptotic cell death in a variety of cells, there are no published data regarding whether human leiomyomas express Bcl-2 protein. In the present study, we examined the expression of Bcl-2 protein in leiomyomas in comparison with that in the normal myometrium using an immunohistochemical method and immunoblot analysis with a monoclonal antibody to human Bcl-2 protein. Furthermore, we investigated whether sex steroid hormones could influence the levels of Bcl-2 protein expression in leiomyoma cells cultured in vitro under serum-free, phenol red-free conditions. Immunohistochemical staining for Bcl-2 protein was prominent in leiomyoma cells, but was scarcely present in normal myometrial smooth muscle cells. The expression of Bcl-2 protein in leiomyoma cells was most abundant in the secretory, progesterone-dominated, phase of the menstrual cycle, but was less abundant in the proliferative phase of the menstrual cycle. Western blot analyses of leiomyoma and myometrium tissue extracts revealed that Bcl-2 protein, with a molecular mass estimated at approximately 26 kDa, was abundantly present in leiomyoma tissue extracts, but was undetectable in normal myometrial tissue extracts. In monolayer cultures of uterine leiomyoma cells under a serum-free condition, the addition of progesterone (100 ng/mL) resulted in a striking increase in Bcl-2 protein expression in the cultured leiomyoma cells relative to that in control cultures, whereas the addition of 17 beta-estradiol (10 ng/mL) resulted in a reduction in Bcl-2 protein expression in the cells. The concentrations of sex steroids used were within the physiological tissue concentrations found in leiomyomas and myometrium. The present results suggest that the abundant expression of Bcl-2 protein may have a molecular basis characteristic of leiomyomas in the human uterus and that progesterone may play a vital role in the enhanced expression of Bcl-2 protein in human uterine leiomyoma cells.
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PMID:Increased expression of Bcl-2 protein in human uterine leiomyoma and its up-regulation by progesterone. 898 76


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