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

Proteins encoded by bcl-2 family genes are important regulators of programmed cell death and apoptosis. Alterations in the expression of these apoptosis-regulating genes can contribute to the origins of cancer, as well as adversely influence tumor responses to chemo- and radiotherapy. Using antibodies specific for the Bcl-2, Bax, Bcl-X, and Mcl-1 proteins in combination with immunohistochemical methods, we examined for the first time the expression of these bcl-2 family genes in 64 cases of adenocarcinoma of the prostate, including 10 Gleason grade 2 to 4 tumors, 21 grade 5 to 7 tumors, 17 grade 8 to 10 tumors, 8 lymph node metastases, and 8 bone metastases. In addition, 24 cases of prostatic intraepithelial neoplasia (PIN) or PIN coexisting with carcinoma were also evaluated. All immunostaining results were scored with regard to approximate percentage of positive tumor cells and relative immunostaining intensity. Expression of the anti-apoptotic protein Bcl-2 was present in 16 of 64 (25%) adenocarcinomas and tended to be more frequent in high grade tumors (Gleason grade 8 to 10; 41%) and nodal metastases (38%) than in lower grade (Gleason 2 to 7) primary tumors (16%; P < 0.05). Bcl-X was expressed in all 64 (100%) tumors evaluated. Bcl-X immunointensity was generally stronger in high grade primary tumors (grade 8 to 10) and metastases compared with PIN and low grade neoplasms (P < 0.0001). In addition, the proportion of specimens with > 50% Bcl-X-immunopositive tumor cells also was higher in advanced grade primary tumors (Gleason 8 to 10) and metastases than in PIN and low grade tumors (Gleason 2 to 7; P < 0.005). The anti-apoptotic protein Mcl-1 was expressed in 52 of 64 (81%) tumors, compared with only 9 of 24 (38%) cases of PIN (P < 0.001). In addition, the percentage of Mcl-1-positive cells was typically higher in Gleason grade 8 to 10 tumors and metastases than in PIN or lower grade tumors (P = 0.025). In contrast, the pro-apoptotic protein Bax was expressed in all prostate cancers evaluated, with high percentages of immunopositive cells and strong immunointensity typically occurring regardless of tumor grade. The findings suggest that expression of several anti-apoptotic members of the bcl-2 gene family, including bcl-2, bcl-X, and mcl-1 increases during progression of prostate cancers, a finding that may be relevant to the hormone-insensitive, metastatic phenotype of most advanced adenocarcinomas of the prostate.
 ...
PMID:Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. 862 25

Chemotherapeutic agent-induced DNA cleavage gives rise to apoptosis in a subpopulation of SK-N-SH human neuroblastoma cells; the remaining cells undergo Schwann cell-like differentiation. Like other neural crest and primitive neurectodermal tumor-derived cell lines, SK-N-SH cultures contain cells of neural (N-type) and epithelial (substrate-adherent, or S-type) phenotypes. Using isolated N-type and S-type cells from neuroblastoma, medulloblastoma, melanoma and glioma cell lines, we demonstrate that the determinants of the response to DNA cleavage are intrinsic properties of the cell. Furthermore, using a series of analogues of enediyne deoxyribonucleic acid (DNA) cleaving agents, we show that the molecular target of these agents is likely to be the same in N- and S-type cells, implying that the difference in response characteristics is a function of different distal pathways that are triggered by DNA cleavage. We demonstrate that the concentration of the DNA damaging agent used, and not the specific characteristics of the damage it produces, is the trigger for production of the cellular response. Response type does not correlate with previously published values for expression of the apoptosis modulators Bcl-2, Bcl-XL, wildtype p53, or, in medulloblastoma lines, p75.
 ...
PMID:Determinants of the response of neuroblastoma cells to DNA damage: the roles of pre-treatment cell morphology and chemical nature of the damage. 862 28

Programmed cell death (apoptosis) plays a major role in embryogenesis, in mature organ homeostasis and in many disease states including cancer. Apoptosis occurs as an orderly cell-intrinsic suicide program regulated by a family of genes related to Bcl-2. Here, we describe the cloning and molecular characterization of a gene homologous to Bcl-2 from a human glioma. This gene named BRAG-1 (for brain-related apoptosis gene) has an open reading frame that encodes for a protein of 31 kDa sharing significant sequence homology with the Bcl-2 family of genes in the BH1 and BH2 regions. Northern blot analyses revealed that BRAG-1 is expressed in human gliomas as a 1.8 kb message. This gene, interestingly, was found to be expressed predominantly in normal human brain as a 4.5 kb transcript which is different in size from the message found in tumor tissues. These results suggest that BRAG-1 may be rearranged in human gliomas leading to its over-expression as a truncated transcript. Utilizing a bacterial expression vector, we produced BRAG-1 protein which was found to cross-react with a Bcl-2 monoclonal antibody, further suggesting structural and immunological similarity to Bcl-2.
 ...
PMID:Identification of a novel Bcl-2 related gene, BRAG-1, in human glioma. 864 11

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.
 ...
PMID:Expression of the cell death-inducing gene bax in carcinomas developed from the follicular cells of the thyroid gland. 867 2

We investigated expression of Bcl-2, mutations in p53, and K-ras oncogene in 51 resected human non-small cell lung cancers. The studies were designed to test for the possibility of cooperativity between these oncogenes and p53 in the pathogenesis of lung cancer. An inverse relationship was found between expression of Bcl-2 and mutant p53 by immunohistochemistry (P < 0.01; Fisher exact test), suggesting that either Bcl-2 overexpression or mutations in p53 may fulfill a critical function in the pathogenesis of human non-small cell lung cancers. Tumors that harbored K-ras codon 12 mutations seldom had p53 mutations or overexpressed Bcl-2. Statistical analysis of these data showed that mutations in p53 and K-ras or overexpression of Bcl-2 and mutations in K-ras occurred at a frequency that could be explained only by chance [P > 0.1 in each case (Fisher exact tests)]. This suggests that cooperativity between mutant K-ras and mutant p53 or mutant K-ras and overexpressed Bcl-2 is not a common mechanism in the pathogenesis of human non-small cell lung cancers.
 ...
PMID:Overexpression of Bcl-2 and mutations in p53 and K-ras in resected human non-small cell lung cancers. 867 21

Activated murine peritoneal macrophage cytotoxicity against P815 tumor cells has been shown to be mediated by the reactive nitrogen intermediates (RNI) produced by macrophages from L-arginine through nitric oxide (NO) synthase. Previous results from this laboratory indicated that NO-dependent killing of P815 fulfilled the criteria for apoptotic death. Work by others, in turn, demonstrated that the product of the bcl-2 gene confers protection against various inducers of apoptosis, including reactive oxygen intermediates. Experiments were performed to determine whether Bcl-2 could equally protect sensitive cells from RNI-dependent apoptosis within the context of a relevant biologic system such as the delivery of such RNI by activated macrophages. Results demonstrated that transfection of P815 cells with the human bcl-2 gene confers immunity from RNI-dependent, macrophage-mediated cytotoxicity. In contrast with wild-type or mock-transfected P815 cells, which do not contain detectable Bcl-2, bcl-2-transfected cells showed minimal DNA fragmentation and cell membrane failure when cocultured with activated macrophages. Additional findings indicate that Bcl-2 affords the transfected cells almost complete resistance to the DNA-fragmenting effects of chemically generated NO or H202 and partial protection from their cytolytic effects. These findings are consistent with the hypothesis that tumor cells expressing bcl-2 may escape destruction by macrophage-dependent immune surveillance mechanisms.
 ...
PMID:B cell lymphoma-2 transfected P815 cells resist reactive nitrogen intermediate-mediated macrophage-dependent cytotoxicity. 868 26

Tests for estrogen (ER) and progesterone (PR) receptors, c-erbB-2, p53 and Bcl-2 were made on paraffin sections of thirty-three cases of invasive micropapillary carcinoma (MPCa) of the breast. The relations between these proteins and general parameters and the patients' evolution, were analyzed and their statistical significance determined by Fisher's exact test. Follow up was available on twenty one patients of whom thirteen were alive after a mean of sixty months. Tumor size, metastatic nodes, c-erbB-2 and Bcl-2 all showed higher values in the dead patient group, but only nuclear grade and extensive lymphatic vessel invasion (LVI) were statistically significant prognostic factors. Hormone receptors and oncogenes were positive in quite similar figures to those of common breast cancers (NOSCa) and offered supplementary information about differentiation and cell atypia of individual cancers. Accordingly, ER (72.7%), PR (45.4%) and Bcl-2 (69.6%) were directly interrelated and inversely related with nuclear grade, mitotic grade, c-erbB-2 (36.3%) and p53 (12.1%). In conclusion, MPCa is a lymphotropic cancer phenotype whose prognosis can be influenced by known prognostic factors, including molecular. The lack of discriminative power between MPCa and NOSCa of ER, PR, c-erbB-2, p53, and Bcl-2 reinforces the importance of recognizing this particular type of cancer.
 ...
PMID:Estrogen and progesterone receptors, c-erbB-2, p53, and Bcl-2 in thirty-three invasive micropapillary breast carcinomas. 868 38

The expression of the apoptosis-regulating genes Bcl-2, Bcl-x, Bax, Mcl-1, and p53 analyzed in 4 cases of human immunodeficiency virus (HIV)-associated Hodgkin's disease, in 36 cases of HIV-related non-Hodgkin's lymphomas (NHLs), and in 109 cases of non-HIV-related NHLs by using immunohistochemistry. HIV-associated Hodgkin's disease samples were positive for all markers. For the HIV-related NHL samples, 36, 66, 88, 100, and 94% of the cases were Bcl-2, Bcl-x, Bax, Mcl-1, and p53 were found to be expressed in 69, 65, 82, 83, and 42%, respectively. No significant differences were observed in Bax and Mcl-1 staining between HIV-unrelated NHLs of B cell and T cell types. In contrast, Bcl-2 was positive in 66/79 (83%) and 10/30 (33%) of B cell and T cell HIV-unrelated NHLs, respectively (P2 < 0.001). Peculiar patterns were observed for hairy cell leukemia (Bax+, Bcl-2+, Mcl-1-) and for anaplastic large cell lymphoma (Bax+, Mcl-1+, Bcl-2-) in HIV-unrelated NHLs. Of interest, all cases with a positive expression of Bax were also found to express either Mcl-1 and/or Bcl-2, suggesting that Mcl-1 and Bcl-2 may counteract the pro-apoptosis function of Bax in vivo by protein-protein interaction within the tumor cell, as demonstrated previously in vitro. These results suggest that apoptosis regulation may have a role in the pathogenesis of some HIV-related and HIV-unrelated NHLs.
 ...
PMID:Immunodetection of apoptosis-regulating proteins in lymphomas from patients with and without human immunodeficiency virus infection. 868 41

Recent advances in molecular biology have revealed various genetic lesions in lung cancer. Mutations of the K-ras gene, amplification or overexpression of myc family genes, erbB2 gene, or bcl2 gene are frequent genetic changes of oncogenes in lung cancer. Inactivation of tumor suppressor genes such as Rb gene, p53 gene, or p16 gene are also seen rather frequently. Furthermore, loss of heterozygosity at certain chromosomal arms such as 3p, 5q, 18q and 22q suggesting inactivation of yet unidentified tumor suppressor genes, also occurs in a significant proportion of lung cancers. Most of these genetic lesions have been reported to be associated with a poor prognostic outcome of the patients. However, great controversy exists as to whether a certain genetic lesion is really a prognostic marker. For example, although about 20 studies have been published, the prognostic implications of the p53 gene for patients with lung cancer still remain unclear. Little is known about the mechanism through which a certain genetic change affects the patient's prognosis. To ultimately improve the prognosis of patients with this deadly disease, definitive studies on which subsequent clinical trials can rely are much awaited.
 ...
PMID:[Genetic abnormalities in lung cancer and their prognostic implications]. 868 34

We review some of the most recent developments concerning three genes involved in human cancer: p53, bcl2 and c-myc. Recent data have demonstrated that the bcl2 gene protects tumor cells from apoptosis induced by a variety of agents, including ionizing radiation, and is thus related to resistance to DNA-damaging therapeutic agents. The p53 tumor suppressor gene, however, has been related with growth arrest, apoptosis and thus with selective sensitivity to the killing effects of ionizing radiation and DNA-damaging drugs. This functional antagonism between the two genes was recently substantiated in molecular terms by demonstration of reciprocal down-regulation due to the presence of a p53-dependent transcription silencer in the untranslated region of the bcl2 gene. Growth arrest in the G1 phase of the cell cycle and induction of apoptosis are two distinct and dissectable functions of p53: bcl2 is able to antagonize the induction of apoptosis by p53, but not the growth arrest in G1. However, coexpression of bcl2 and of the oncogene c-myc efficiently antagonizes effects of p53 on G1 arrest and apoptosis, thus suggesting a cooperation between the two oncogenes. In addition, c-myc disrupts other functions of genetic control in the early G1 phase of the cell cycle including the expression of D1 cyclin. We believe that knowledge of the functional/molecular interactions between these three genes involved in human cancer is a fundamental prerequisite to improve the knowledge on prognosis and to design innovative therapeutic approaches.
 ...
PMID:Role of three cancer "master genes" p53, bcl2 and c-myc on the apoptotic process. 869 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>