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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 proto-oncogene prevents apoptosis in many conditions. First detected in lymphomas, it has been also described in non-lymphoid tissues. The immunohistochemical distribution of bcl-2 protein in 100 neuroepithelial tumors is presented. Bcl-2 was positive in some neurons of normal nervous tissue, in reactive astrocytes and variably in all neuroepithelial tumor. The reaction product was either diffuse or granular, due to bcl-21 protein localization on cytoplasmic, nuclear and mitochondrial membranes. The positivity was high in medulloblastomas and in astrocytic tumors. In the latter, the strongest staining was found in cells retaining the astrocytic aspect. Oligodendroglial cells were minimally stained. No correlation of bcl-2 staining with survival was found in each tumor type. The interpretation of the results is based on the one side on the constitutive role played by bcl-2 in the nervous tissue and its neoplastic derivatives. On the other side, in tumors bcl-2 acts by preventing tumor cells from undergoing apoptosis. BCl-2 expression in brain tumors, therefore, receives a dual interpretation. For this reason and for the lacking of correlation with survival, bcl-2 expression cannot be regarded as a prognostic factor.
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PMID:Bcl-2 distribution in neuroepithelial tumors: an immunohistochemical study. 869 31

Control of transformed cells by neighbouring normal cells is known since the beginning of transformation studies in vitro. The classical explanation for this phenomenon is based on proliferation inhibition of transformed cells by normal cells. We extend this model by presenting data that show that TGF-beta-treated normal cells can eliminate transformed cells by induction of apoptosis. Both the TGF-beta-induced signal pathway in normal cells, leading to the production of a short-lived apoptosis-inducing factor, as well as the specific interaction of this factor with transformed cells depend on the action of reactive oxygen species. Sensitivity to induction of apoptosis seems to be a common feature associated with the transformed state, independent of the originally transforming principle. Therefore, tumor development should require either interference with the process of elimination or acquisition of resistance against it. We discuss experimental evidence for interfering substances, such as antioxidants, as well as for genetic systems that protect transformed cells from the negative effects of their cellular environment, such as Bcl-2 or papilloma viruses. These findings, as well as the general resistance of exvivo tumor cells against induction of apoptosis are in line with the novel model of control of tumor progression presented by us in this review.
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PMID:Elimination of transformed cells by normal cells: a novel concept for the control of carcinogenesis. 872 Apr 67

Analysis of programmed cell death (apoptosis), of bcl-2, a critical regulator of this process, and of the proliferative fraction may provide detailed information on the biologic characteristics of tumor cell populations. To investigate the potential role of these parameters in assessing mammary carcinoma, we adapted flow cytometric procedures for concurrent measurement of apoptosis, bcl-2 expression, and cell proliferation in 54 primary breast carcinomas and correlated the findings with traditional clinicopathologic information. Overall, a significant inverse relationship between apoptosis levels and bcl-2 expression was observed (P = 0.005). Apoptosis levels correlated significantly with DNA aneuploidy (P = 0.03) and S + G2M fractions (P = 0.005) of these tumors. A significant correlation between bcl-2 expression and estrogen receptor positivity (P = 0.05) and DNA diploidy (P = 0.02) was noted. Bcl-2 expression, however, was inversely correlated with S + G2M fractions (P = 0.001). We conclude that analysis of apoptosis and bcl-2 by flow cytometry allows further characterization of tumor cell populations that may be useful for prognostic and therapeutic management of breast carcinoma.
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PMID:Flow cytometric analysis of apoptosis and bcl-2 in primary breast carcinomas: clinical and biological implications. 872 60

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

For determination of the cellular distribution of bcl-2 expression in lung cancer and clarification of its correlation with cell neuroendocrine differentiation, Bcl-2 immunostaining was carried out on a large series of formalin-fixed, paraffin-embedded lung cancer samples, and four general neuroendocrine marker and seven peptide hormone stainings were carried out on all Bcl-2-positive squamous cell carcinomas and adenocarcinomas of the lung as well as on 8 pulmonary neuroendocrine carcinomas histologically diagnosed. In addition, 3 small cell lung cancer cell lines were studied by Western blotting. Neuroendocrine differentiation in Bcl-2-negative squamous cell carcinomas and adenocarcinomas was examined with chromogranin A and alpha-subunit of Go protein stainings. Bcl-2 protein was detected in 104/111 small cell carcinomas, 8/8 neuroendocrine carcinomas, 0/6 typical (well differentiated) carcinoids, 23/64 squamous cell carcinomas, 4/65 adenocarcinomas, and all 3 small cell lung cancer cell lines. All 8 neuroendocrine carcinomas, 11 of the Bcl-2-positive squamous cell carcinomas, and all 4 Bcl-2 positive adenocarcinomas expressed multiple neuroendocrine markers. The distributions of Bcl-2 and neuroendocrine marker immunoreactivity closely paralleled each other on consecutive sections. In squamous cell carcinomas, Bcl-2-positive cells could be roughly subdivided into those with neuroendocrine differentiation features, usually demonstrating intense Bcl-2 staining, with basaloid tumor cells usually expressing weak to moderate Bcl-2 staining. The present study clearly shows Bcl-2 protein expression to be remarkably differentially regulated according to histological types of lung cancers and to appear to quite likely be closely associated with neuroendocrine differentiation of tumor cells, indicating that bcl-2 is importantly involved in cell development and differentiation, in addition to protecting cells from apoptosis. Bcl-2 might be usable as a neuroendocrine marker in lung cancers and possibly also in neural-crest-derived tumors.
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PMID:Bcl-2 protein expression in lung cancer and close correlation with neuroendocrine differentiation. 877 38

CD95 (APO-1/Fas) is a member of the superfamily that includes the nerve growth factor and tumor necrosis factor receptors, OX40, CD27, CD30, and CD40. Present on a minority of resting blood lymphocytes, CD95 expression is upregulated on activated T and B lymphocytes and natural killer cells, where binding of the antigen by anti-Fas and anti-APO-1 antibodies has been shown to induce apoptosis. This CD95-mediated apoptosis is at least partially inhibited by expression of the Bcl-2 protooncogene. To evaluate possible roles of CD95 and Bcl-2 in growth regulation of lymphoid neoplasms, we studied by immunohistochemistry the expression of CD95 and Bcl-2 in 67 B- and 5 T-cell lymphomas, and 10 cases of Hodgkin's disease. In all, 29 B and 2 T cell lymphomas, and 9 cases of Hodgkin's disease expressed CD95. Compared with diffuse large B-cell and Burkitt-like lymphomas, lowgrade B-cell lymphomas more frequently expressed CD95 (52% versus 26%; P < .005). None of the B-cell small lymphocytic lymphomas or mantle cell lymphomas expressed CD95, whereas the majority of follicle center lymphomas, extranodal marginal zone B-cell lymphomas, and immunocytomas were CD95+. Of the 29 CD95+ B-cell lymphomas, only 33% of the high-grade group coexpressed Bcl-2, compared with 87% of the low-grade group (P < .04). Two of three peripheral T-cell lymphomas--including one anaplastic large cell lymphoma--expressed CD95. Staining for CD95 was seen in 9 of 10 cases of Hodgkin's disease. The infrequent expression of CD95 in high-grade B-cell lymphomas suggests an association between loss of CD95 expression/function and a more aggressive tumor grade. Whereas frequent coexpression of Bcl-2 with CD95 may protect low-grade B-cell lymphomas against CD95-mediated apoptosis, in the high-grade group such coexpression is infrequent, and other regulators besides Bcl-2 may be involved in modulating the apoptosis signal delivered by CD95.
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PMID:Expression of CD95 antigen and Bcl-2 protein in non-Hodgkin's lymphomas and Hodgkin's disease. 877 39

Several recently identified proteins such as Bcl-2 and Bcl-x have been found to regulate programmed cell death (i.e., apoptosis). In this report, we examined the levels of expression of proteins that can either prevent apoptosis (i.e., Bcl-2 or the long form of Bcl-x, designated Bcl-x1) or promote apoptosis (i.e., Bax or the short form of Bcl-x, designated Bcl-xs) in proliferating benign and malignant endothelial cells (ECs). In normal skin with quiescent ECs, no detection by immunohistochemical staining was observed for Bcl-xL, Bcl-xs, or Bcl-2. However, in diseased skin samples that feature a prominent angiogenic response such as in psoriasis or pyogenic granulomas, the proliferating ECs markedly overexpressed Bcl-xL, with little to no Bcl-2. In an acquired-immune-deficiency-syndrome-related neoplasm, Kaposi's sarcoma, the spindle-shaped tumor cells also overexpressed Bcl-xL compared with Bcl-2. These in vivo studies were extended in vitro using cultured ECs and Kaposi's sarcoma tumor cells that were examined by flow cytometry and immunoblot analysis. Both cultured ECs and Kaposi's sarcoma tumor cells express significantly higher levels of Bcl-xL than Bcl-2. Such overexpression of cell survival gene products may contribute to prolonging the longevity of EC-derived cells in several different benign and neoplastic skin disorders that are characterized by a prominent angiogenic tissue response.
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PMID:Kaposi's sarcoma tumor cells preferentially express Bcl-xL. 878 Mar 84

Recent work demonstrated that B7 expression by tumor cells can enhance antitumor immune responses. However, the B7 molecule is expressed abundantly on most non-Hodgkin's B-cell lymphomas and solid lymphoid tumors. How these tumor cells escape from immune surveillance mechanisms remains unclear. Lately, it has become clear that bcl-2 oncogene is overexpressed in a wide variety of human cancers and renders tumor cells more resistant to cytolytic T-cells (CTL) mediated cytotoxicity. We cloned B7 and B7/Bcl-2 transfectants and compared their susceptibilities to a human natural killer (NK) cell line and normal NK cells. The results demonstrate that Bcl-2 oncoprotein in tumor cells blocks B7-induced cytolysis mediated by a NK cell line and NK cells. Thus, they suggest that Bcl-2 oncoprotein plays a role in tumor avoidance of effective antitumor cytotoxicity.
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PMID:BCL-2 inhibits B7-induced MHC-unrestricted cytolysis mediated by a human NK cell line. 880 52

Bcl-2 is a protooncogene thought to play a role in oncogenesis by inhibiting programmed cell death. It may interact with p53, a tumor-suppressor gene which induces apoptosis in certain circumstances. We have studied these gene products by immunohistochemistry in 15 cases of Merkel cell carcinoma, a tumor characterised by prominent apoptosis. Five cases showed moderate/strong staining for p53, with moderate/strong bcl-2 staining in 10 patients. In seven cases abundance of p53 and bcl-2 expression was mutually exclusive. Two patients died within 1 year of diagnosis and six had nodal recurrences. Gene expression and survival appear unrelated. The role of Bcl-2 and p53 in tumorigenesis is complicated and may be inter-related with other genes known to be involved in programmed cell death.
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PMID:Expression of bcl-2 and p53 in Merkel cell carcinoma. An immunohistochemical study. 880 61

We have developed an animal tumor model system to study the effects of c-Myc activation on apoptosis induction in vivo. Tumors were generated in SCID mice from Rat-1 fibroblasts that constitutively express an inactive c-Myc-estrogen receptor fusion protein (T.D. Littlewood et al, Nucleic Acids Res., 23: 1686 -1690, 1995), which is activated in vivo by the administration of 4-hydroxytamoxifen in time release pellets. We demonstrate that activation of c-Myc results in a substantial increase in the number of apoptotic tumor cells and that this apoptosis is predominant in regions of tumor hypoxia. c-Myc-induced apoptosis of hypoxic cells is inhibited in tumors that overexpress the human Bcl-2 protein. Bcl-2, however, does not prevent p53 protein accumulation or the down-regulation of the cyclin-cdk inhibitor p27 protein following c-Myc activation by 4-hydroxytamoxifen. This result suggests that Bcl-2 does not affect c-Myc function directly but acts downstream of c-Myc to inhibit apoptosis. We propose that the ability of activated c-Myc to enhance cellular proliferation might contribute to the genesis of early neoplasms that are held in check by the alternate ability of c-Myc to induce apoptosis of cells that have outgrown their supply of oxygen or other factors associated with hypoxic regions of solid tumors. Secondary genetic lesions downstream of c-Myc that suppress the apoptotic potential of tumor cells, such as Bcl-2 overexpression, might play an important role in the malignant progression of these tumors because they would disrupt the balance between apoptosis and proliferation initiated by c-Myc deregulation.
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PMID:Modulation of c-Myc activity and apoptosis in vivo. 881 14


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