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)

The Bcl-2 proto-oncogene regulates cell survival by antagonizing events that lead to apoptotic cell death and has been reported to be expressed in situ in lymphoid tissues, glandular epithelium, neurons, and basal epidermal cells. When we performed immunostaining on cryostat sections of normal skin, anti-Bcl-2 reactivity was confined to scattered dendritic cells in the basal epidermal layer. Double-staining experiments showed that the Bcl-2+ cells were positive for vimentin but negative for cytokeratins, CD1a, and CD45 antigens, excluding keratinocytes and Langerhans cells as possible candidates for constitutive Bcl-2 expression. Bcl-2+ epidermal cells also reacted with the monoclonal anti-melanocyte antibody NKI/beteb, and were absent from lesional skin in vitiligo, confirming that they represented epidermal melanocytes. Western blot analysis of cultured melanocytes and melanoma cell lines revealed a 26-kd protein specifically reacting with the anti-Bcl-2 monoclonal antibody. Immunostaining of pigmented lesions revealed strong expression of Bcl-2 by five of five nevocellular nevi and seven of seven melanomas. Our observations demonstrate that, within normal human epidermis, melanocytes are the only cells that express Bcl-2 constitutively and that Bcl-2 is expressed in benign and malignant pigmented tumors of the skin in situ.
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PMID:Human melanocytes and melanoma cells constitutively express the Bcl-2 proto-oncogene in situ and in cell culture. 788 47

The Caenorhabditis elegans gene ced-9 and the human proto-oncogene bcl-2, both of which protect cells from programmed cell death, are members of the same gene family. ced-9 and bcl-2 were discovered because of the effects of dominant gain-of-function mutations. Such bcl-2 mutations, which are commonly found in follicular lymphoma, are translocations that result in over-expression of a normal Bcl-2 protein in B cells. Here we report that, by contrast, the ced-9(n1950) gain-of-function mutation affects the open reading frame of ced-9 and results in a glycine-to-glutamate substitution in a region highly conserved among all ced-9/bcl-2 family members. We conclude that this glycine has an important function in ced-9 regulation, and we suggest that alteration of this glycine in other members of the ced-9/bcl-2 family might lead to oncogenic activation. We also present genetic evidence suggesting that the CED-9 protein might exist in two distinct forms that have opposite effects on cell death.
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PMID:Activation of C. elegans cell death protein CED-9 by an amino-acid substitution in a domain conserved in Bcl-2. 818 60

Mcl-1, a protein increased early in the differentiation of human myeloblastic ML-1 cells, has sequence similarity to Bcl-2. In the present study, we determined whether Mcl-1 has functional similarity to Bcl-2 by testing its ability to inhibit apoptosis induced by c-Myc overexpression. This was carried out using Chinese hamster ovary 5AHSmyc cells which contain the human c-myc proto-oncogene under the control of a heat shock promoter. Heat treatment induces c-Myc overexpression and thus apoptosis as determined by internucleosomal DNA fragmentation. We transfected 5AHSmyc cells with mcl-1 and found that clones expressing the introduced Mcl-1 protein exhibited reduced DNA fragmentation. Mcl-1 was also capable of delaying the onset of cell death as judged by loss of membrane integrity, although it could not provide complete protection from c-Myc overexpression. Thus, Mcl-1 has functional homology to Bcl-2 in that Mcl-1 can enhance cell viability under conditions that otherwise cause apoptosis.
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PMID:Mcl-1, a member of the Bcl-2 family, delays apoptosis induced by c-Myc overexpression in Chinese hamster ovary cells. 798 27

R-ras is a member of the ras family of small GTPases that associates with the apoptosis-suppressing proto-oncogene product Bcl-2. Using the yeast two-hybrid system we provide evidence for an interaction between R-ras and the Raf-1 kinase. This interaction requires only the N-terminal regulatory domain (amino acids 1-256) of Raf-1, and is observed with both the wild type and a constitutively active R-ras mutant, but not with a deletion mutant that lacks the potential effector domain or a mutant of R-ras impaired for GTP binding. Moreover, using an in vitro binding assay we show a direct GTP-dependent interaction of purified R-ras with a purified Raf-1 fragment corresponding to the proposed 81-amino-acid H-Ras-binding domain of Raf-1 (amino acids 51-131). Taken together, these data indicate that R-ras may exert its biological effect by means of modulating the activity of the Raf-1 kinase as its direct downstream effector.
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PMID:The Ras-related protein R-ras interacts directly with Raf-1 in a GTP-dependent manner. 800 32

The bcl-2 gene is a unique proto-oncogene that blocks apoptosis; its product is localized on the inner mitochondrial membrane. In non neoplastic human lymphoid tissues, bcl-2 protein is strongly expressed in the small recirculating lymphocytes of the follicular mantle zone; it is expressed less intensely in T-cell areas, and is almost absent from germinal center cells. Bcl-2 mRNA, in contrast to bcl-2 protein, is strongly expressed on most of the latter cells, a similar phenomenon also being observed in peripheral blood lymphocytes (PBL). Resting PBL express both bcl-2 mRNA and protein, while most lymphoblasts in mitogen-stimulated PBL cultures lose bcl-2 protein and become apoptotic, despite expressing higher levels of mRNA. Posttranscriptional regulation of the bcl-2 gene may cause this paradoxical down-regulation of bcl-2 protein and may play an important role in the clonal selection of lymphocytes. Bcl-2 protein is frequently expressed in follicular lymphomas bearing the t(14;18) chromosomal translocation, but it is also widely expressed in many other B- and T-cell lymphomas without bcl-2 rearrangement, showing that mechanisms other than t(14;18) translocation may deregulate bcl-2 expression. Many lymphoid and myeloid cell lines also express bcl-2 protein with no correlation being shown with differentiation stage. Thus, it is conceivable that bcl-2 protein may play a role in the oncogenesis of many hematolymphoid malignancies by interfering with programmed cell death, in concert with other oncogenes or tumor suppressor genes.
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PMID:Expression of Bcl-2 protein and Bcl-2 mRNA in normal and neoplastic lymphoid tissues. 802 26

During an immunohistochemical study of the distribution of the Bcl-2 proto-oncogene product in frozen sections of normal human skin, a hitherto unrecognized strong reactivity with melanocytes was observed. This prompted us to study Bcl-2 expression in a variety of pigment lesions. In nevocellular nevi, immunoreactivity gradually diminished or even disappeared toward the deeper dermal component. In malignant melanomas of all stages and histological subtypes, the neoplastic cells expressed Bcl-2 oncoprotein, the most intense positivity being restricted to cells in the radial growth phase. Cutaneous and lymph node metastases of malignant melanomas were negative or showed only weak and focal reactivity. The specificity of the staining was confirmed by Western blotting of tissue lysates. The loss of Bcl-2 expression in the deeper parts of nevi may offer an explanation for the "maturation" and final disappearance of dermal nevocellular nevi. The expression of Bcl-2 oncoprotein by malignant melanomas adds these neoplasms to a growing list of tumors expressing this oncoprotein. Bcl-2 in malignant melanoma may play a role in tumor development by sparing the cells from apoptotic death (and thereby exposing them to secondary events) or through cooperation with other oncogenes. The lack of reactivity in metastatic melanoma suggests that mechanisms other than Bcl-2 are involved in the survival and growth of metastatic melanoma cells.
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PMID:Bcl-2 expression in human melanocytes and melanocytic tumors. 805 90

The protein encoded by the Bcl-2 proto-oncogene has been shown to inhibit programmed cell death and has been primarily studied in hematolymphoid malignancies. Recent work ahs elucidated Bcl-2 expression in nonhematolymphoid malignancies of the lung, prostate, and nasopharynx. Studies of Bcl-2 expression in prostate carcinoma have suggested that its expression may be related to hormonal control. To determine its presence and possible significance in breast carcinoma, a malignancy in which therapy is influenced by hormone receptor status, we used a monoclonal antibody directed against the Bcl-2 gene product to examine Bcl-2 immunoreactivity in a series of paraffin-embedded primary breast tumors. Benign breast tissue showed Bcl-2 positivity in the basal layer and in superficial cells. Twenty-four of 41 (58%) carcinomas were Bcl-2 positive. Staining for Bcl-2 was equivocal in two cases. We identified a strong correlation between Bcl-2 expression and hormone receptor positivity as 23 of 24 (96%) cases that were Bcl-2 positive were estrogen receptor (ER) positive (P = 0.0001) and 21 of 24 (87.5%) were positive for progesterone receptor PR (P = 0.0001). Of 15 Bcl-2-negative cases, 14 (93%) were ER negative and all were PR negative. One case of mucinous carcinoma was ER positive and Bcl-2 negative. Grade 1 and 2 tumors (Scarff-Bloom-Richardson scale) were almost three times as likely to be Bcl-2 positive (90%) as grade 3 tumors (33%) (P = 0.0057). Bcl-2 reactivity appears to be more prevalent in well-differentiated tumors, suggesting that its presence may diminish with loss of differentiation, a hypothesis that is further supported by a subset of cases that were ER negative, Bcl-2 negative, and of poor histological grade. These may be tumors that do not require Bcl-2 inhibition of apoptosis and respond to hormonally independent proliferation factors. Our findings support the hypothesis that Bcl-2 expression may be related to hormonal regulation in breast carcinoma.
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PMID:Bcl-2 immunoreactivity in breast carcinoma correlates with hormone receptor positivity. 808 38

Bcl-2 proto-oncogene is expressed in normal lymphoid tissues and its role has been suggested to involve the selection of B and T cells. Here we report three-color flow cytometric studies on the expression of bcl-2 protein in the thymus and periphery. Bcl-2 was expressed in the majority of T and B cells and down-regulated only in the CD1+, CD3- to low, CD4+8+ thymocytes, and the B cells that are in cell cycle in the tonsil and lymph node. In contrast, the CD2+, CD1-3-4-8-19-, early T cells, and mature single positive cells in the thymus, as well as the tonsilar and lymph node T cells, irrespective of their cell cycle status, expressed bcl-2. These results are consistent with the notion that bcl-2 is down-regulated in the T and B cells that are in the process of generating new antigen receptors and subject to subsequent positive selection.
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PMID:Bcl-2 expression in the thymus and periphery. 818 Oct 70

Bcl-2 is a proto-oncogene initially described in the (14;18) translocation in follicular lymphoma. It has been shown to prolong cell survival by preventing apoptosis. Endometrium undergoes rapid proliferation and differentiation under hormone control and is thus an excellent model to study the hormone dependency of Bcl-2 expression. We studied Bcl-2 expression by an immunohistochemical method in 53 samples of normal endometrium randomly distributed throughout the menstrual cycle, as well as five samples of hyperplastic endometrium. Bcl-2 staining predominated in glandular cells and peaked at the end of the follicular phase. Bcl-2 expression disappeared at the onset of secretory activity. The stroma, surface lining epithelium and arterial vessels also displayed cyclic variations in Bcl-2 expression. These results strongly suggest hormone-dependent regulation of Bcl-2 expression, which could play an important role in tumorigenesis.
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PMID:Bcl-2 expression in normal endometrium during the menstrual cycle. 820 60

The proto-oncogene bcl-2 inhibits apoptotic and necrotic neural cell death. Expression of Bcl-2 in the GT1-7 neural cell line prevented death as a result of glutathione depletion. Intracellular reactive oxygen species and lipid peroxides rose rapidly in control cells depleted of glutathione, whereas cells expressing Bcl-2 displayed a blunted increase and complete survival. Modulation of the increase in reactive oxygen species influenced the degree of cell death. Yeast mutants null for superoxide dismutase were partially rescued by expression of Bcl-2. Thus, Bcl-2 prevents cell death by decreasing the net cellular generation of reactive oxygen species.
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PMID:Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. 823 59


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