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)

Apoptosis has been found to play a crucial role in the pathogenesis and prognosis of many human diseases. The pathogenesis of gestational trophoblastic disease (GTD), which encompasses hydatidiform moles (HMs) and choriocarcinomas (CCAs), is not fully understood. Prognostic indicators of HM have also been scanty. In this study, we investigated apoptotic activity and the expression of two apoptosis regulatory genes, Bcl-2 and Bax, in an attempt to determine the role of apoptosis in GTD. Formalin-fixed paraffin-embedded tissue of 33 normal placentas, 14 spontaneous abortions, 14 partial moles, 34 complete moles, and eight CCAs were examined. Apoptotic activity was assessed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. Quantitative assessment of apoptotic index (AI) was calculated as a percentage of TUNEL-positive nuclei. Expression of Bcl-2 and Bax were assessed immunohistochemically. Extensive apoptosis was located in syncytiotrophoblasts, cytotrophoblasts, and villous stromal cells in all HM cases. Apoptosis was detected at a much lower level in spontaneous abortions and normal placentas. Moreover, in normal placentas, TUNEL positive nuclei were exclusively found in syncytiotrophoblasts. AIs were significantly different among various categories of trophoblastic lesions (P < .001) in an ascending order: normal placentas less than spontaneous abortions less than CCAs less than HMs. Furthermore, AIs of those cases that spontaneously regressed was statistically higher than those that developed persistent trophoblastic disease requiring chemotherapy. AIs of trophoblastic lesions in general inversely correlated with Bcl-2 expression (P < .001), but no significant correlation was found between AI and Bax expression (P > .5). We conclude that AI may be a useful prognostic marker for clinical progress of HMs. Bcl-2 expression is probably regulating apoptosis in normal placentas and GTD, whereas Bax expression is not. The difference in AI and Bcl-2 expression between non-molar placentas and HMs offers a potential adjunctive diagnostic tool to distinguish the two entities.
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PMID:Apoptosis in gestational trophoblastic disease is correlated with clinical outcome and Bcl-2 expression but not Bax expression. 1057 99

The apoptosis-inducer Fas and the apoptosis-suppresser Bcl-2 are members of the tumor necrosis factor receptor and Bcl-2 gene superfamilies, respectively. Bcl-2 is overexpressed in hormonally refractory prostate cancer. Fas is expressed in several prostatic carcinoma cell lines but its in vivo expression in normal prostate and in prostate cancer is poorly understood. Formalin-fixed tissue sections from 10 benign prostatic hyperplasias, 10 low-grade and 10 high-grade organ-confined prostate cancers, and 6 metastatic prostate cancers were evaluated for immunoreactivity with Fas and Bcl-2 monoclonal antibodies. In addition, Fas expression was quantitated by computerized cytometry. The results were compared by one-way analysis of variance followed by Bonferroni tests. In benign prostate samples, Bcl-2 and Fas were expressed on basal cells and secretory cells, respectively. Bcl-2 was not expressed in any organ-confined tumors and only in one of six metastatic tumors (17%). Fas was expressed in all organ-confined tumors and in two of six metastatic tumors (33%). Fas expression was significantly decreased (P < 0.001) in prostate cancer (0.20 pg/cell) compared with benign prostate (0.79 pg/cell). The decrease was inversely related to the malignant grade of the tumors (0.30 pg/cell in low-grade tumors, 0.19 pg/cell in high-grade tumors, and 0.003 pg/cell in metastatic tumors). Based on these preliminary data, decreased expression of Fas appears to be an early molecular event in prostate cancer. The decline begins in low-grade tumors. The lowest expression occurs in metastatic carcinomas, which are often Fas negative. Overexpression of Bcl-2 appears to be a later and unrelated molecular event. Both abnormalities may be implicated in tumor progression by prolonging tumor cell survival.
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PMID:Cytometric analysis of Fas and Bcl-2 expression in normal prostatic epithelium and prostate cancer. 1086 56

Bcl-2 and Bax belong to a family of proteins involved in apoptosis regulation and are believed to reside in the cellular cytoplasm. The authors recently reported interphase nuclear localization of both proteins after immunofluorescence staining of formaldehyde- and methanol-fixed human and rodent cell monolayers. In addition, the authors' data confirmed earlier reports on Bcl-2 immunoreactivity of mitotic chromosomes in human cells. In their experience, nuclear or mitotic staining of Bcl-2, in contrast with cytoplasmic Bcl-2 immunoreactivity, is rarely observed in formaldehyde-fixed, paraffin-embedded breast cancer specimens. Therefore, the authors wondered if nuclear and mitotic Bcl-2 immunoreactivity could be irreversibly reduced by certain fixation procedures, including formaldehyde fixation. Here the authors investigated the effects of various routinely used fixation protocols and antigen retrieval techniques on Bcl-2 and Bax immunoreactivity in monolayers of MCF-7 human breast cancer cells. Whereas nuclear and mitotic immunoreactivity for Bcl-2 was clearly present after formaldehyde and methanol fixation, it was completely absent in cells fixed in acetone, methanol, or formaldehyde alone. In addition, it was found that in particular nuclear and mitotic Bcl-2, and to a lesser extent cytoplasmic Bcl-2 immunoreactivity, decreased after prolonged formaldehyde fixation, whereas Bax immunoreactivity diminished only slightly. Heat-mediated antigen retrieval after prolonged formaldehyde fixation elevated cytoplasmic, but not nuclear and mitotic, Bcl-2 immunoreactivity.
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PMID:Routine formaldehyde fixation irreversibly reduces immunoreactivity of Bcl-2 in the nuclear compartment of breast cancer cells, but not in the cytoplasm. 1127 19

Most follicular lymphomas (FLs) transform to diffuse lymphoma eventually, comprising a significant proportion of diffuse large B-cell lymphoma (DLBCL). Judging by bcl-2 rearrangement (bcl-2R), one third of DLBCLs are believed to be of FL derivation in the Western population. However, bcl-2R is not specific and is not detectable in every case of FL. In East Asia, FL is uncommon but DLBCL is not. The proportion of tumors of FL origin in DLBCL is not known in this region. The coexpression of Bcl-6 and CD10 proteins, a reliable marker to identify germinal center (GC) B-cell lymphoma including FL, was analyzed in primary nodal DLBCLs (n = 104) diagnosed at major hospitals in Seoul during a recent 2-year period, along with well-defined cases (n = 17) of nodal FL as controls. Bcl-2 protein expression (n = 77) was also studied along with bcl-2R (n = 64), by polymerase chain reaction. Formalin-fixed archival specimens were used in all these assays. The Bcl-6/CD10 coexpression was observed in 35 DLBCLs (34%) and 14 FLs (82%), and most of them showed a pattern of Bcl-6 expression similar to that of the GC. Bcl-2 expression or bcl-2R did not correlate with Bcl-6/CD10 coexpression. Histologically, compartmentalizing sclerosis was associated with a high rate of the coexpression (8 of 10). In conclusion, to detect GC B-cell lymphoma in routine biopsy specimens, a pattern of Bcl-6 staining similar to the GC must be identified. Bcl-6+/CD10+ GC B-cell lymphomas thus defined comprised one third of primary nodal DLBCLs in Korea. The incidence rate is similar to that in the West. The reasons for the discrepancy between the incidence of GC B-cell lymphoma and the paucity of the follicular pattern in East Asian subjects warrant further studies.
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PMID:Coexpression of Bcl-6 and CD10 in diffuse large B-cell lymphomas: significance of Bcl-6 expression patterns in identifying germinal center B-cell lymphoma. 1156 25

Immunohistochemical detection of expression of the anti-apoptotic Bcl-2 protein is widely studied as a putative prognostic and predictive factor in various types of cancer. For that purpose, heating for 10 min by microwave (MW) up t o 100 degrees C in citrate buffer, pH 6.0, prior to immunostaining is often used to retrieve Bcl-2 antigens in archival formalin-fixed, paraffin-embedded tissue. We recently reported that Bcl-2 is not only a cytoplasmic protein, but that it is present also in interphase nuclei and that it strongly associates with mitotic chromosomes. Furthermore, we showed that binding of the monoclonal antibody (MAb) #124 with nuclear/chromosomal epitopes is diminished by formaldehyde-based fixatives and cannot be restored by MW treatment for 10 min. Here we report that prolonged MW heating or heating up to 130 degrees C in a high pressure cooker (HPC), despite improved cytoplasmic immunostaining, fails to retrieve nuclear/chromosomal Bcl-2 epitopes recognized by the MAb #124 in human tissues. In contrast, these procedures can retrieve nuclear/chromosomal Bcl-2 epitopes detected by polyclonal #15616E antibodies in rat tissues. The specificity of these epitopes was confirmed by Western blot analysis of tissues treated by MW heating or HPC.
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PMID:Comparison of the effects of microwave heating and high pressure cooking for antigen retrieval of human and rat Bc1-2 protein in formaldehyde-fixed, paraffin-embedded sections. 1222 34

The retinoblastoma (RB) gene product has been shown to restrict cell proliferation, promote cell differentiation, and inhibit apoptosis. Loss of RB function can induce both p53-dependent apoptosis and p53-independent apoptosis; little is known about the mechanisms of RB-regulated p53-independent apoptosis. Here we show that RB specifically activates transcription of the survival gene bcl-2 in epithelial cells but not in NIH 3T3 mesenchymal cells. This transcriptional activity is mediated by the transcription factor AP-2. By monitoring protein-DNA interactions in living cells using formaldehyde cross-linking and chromatin immunoprecipitation, we show that endogenous RB and AP-2 both bind to the same bcl-2 promoter sequence. In addition, we demonstrate that RB and AP-2 also bind to the E-cadherin gene promoter in vivo, consistent with regulation of this promoter by both AP-2 and RB in epithelial cells. This study provides evidence that RB activates bcl-2 and E-cadherin by binding directly to the respective promoter sequences and not indirectly by repressing an inhibitor. This recruitment is mediated by a transcription factor, in this case AP-2. For the first time, our results suggest a direct molecular mechanism by which RB might inhibit apoptosis independently of p53. The results are discussed in a context where RB and Bcl-2 contribute under nonpathological conditions to the maintenance of cell viability in association with a differentiated phenotype, contributing to the tumor suppressor function of RB and playing important roles in normal development.
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PMID:The retinoblastoma protein binds the promoter of the survival gene bcl-2 and regulates its transcription in epithelial cells through transcription factor AP-2. 1239 Nov 56

The aim of our study was to elucidate whether and in a what way applying two slightly different immunohistochemical procedures effects Bcl-2 protein detection as well as its relationship to colorectal cancer clinicopathological features. A series of 74 primary colorectal cancers was investigated for expression of the Bcl-2 protein. Two immunohistochemical procedures: first with antigen retrieval using a microwave (art-), second with antigen retrieval by use pressure pot (art+) pre-treatment, were applied in each cancer case. Formalin-fixed, paraffin embedded tissues were treated with ant-Bcl-2 antibody (Dako No M 0887). Bcl-2 (art+) immunostaining was positive in 48 (64.9%) cases of colorectal cancers whereas Bcl-2 (art-) immunohistochemical reaction was positive only in 15 (20%) colorectal tumours. A significant, positive correlation was observed between Bcl-2 (art+) expression and localization of the tumour in the rectum (p = 0.007). At the same time a statistically significant positive correlation between tumour Bcl-2 (art-) expression and colon tumour pT stage (p = 0.007), rectum tumour differentiation grade (p = 0.04) and Bcl-2 (art-) protein immunostaining in lymph node metastases (p < 0.000001) was observed. This data suggest that the type of procedure for antigen retrieval to detection of Bcl-2 protein by immunohistochemical reaction, changes the study results and should be considered when comparing own results with the literature data.
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PMID:Correlation between colorectal cancer Bcl-2 expression and tumour clinicopathological variables. 1253 67

Prostate cancer (Pca) is the most prevalent cancer diagnosed and the second leading cause of cancer-related deaths among men in the Poland. The present study was designed to analyse the relationship between expression of Bcl-2 protein in prostate cancer (PCa) following radical prostatectomy to chosen anatomoclinical and morfological parameters of the tumours. Tumours from 28 patients were assessed by immunohistochemistry. Tissue sections were fixed in 10% buffered formaldehyde solution, embedded in paraffin and stained immunohistochemically with the anti-human Bcl-2 antibody (Dako/Clon124). The immunolocalization of Bcl-2 was performed using the Labelled Streptavidin Biotin (LSAB) method. No correlation was found between Bcl-2 protein expression and pT stage, lymph node metastases, Gleason score, seminal vesicles invasion, positive or negative resection margins as well as capsular penetration and preoperative PSA serum level.
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PMID:Bcl-2 immunohistochemical detection in prostate cancer. 1253 68

Hepatoblastoma, a childhood tumor of the liver, is composed of epithelial and mesenchymal elements in varying proportions and at various stages of differentiation. The epithelial element recapitulates the stages of hepatocyte development from the primitive blastema through embryonal hepatocytes to fetal hepatocytes. The blastemal or undifferentiated cells have been postulated to represent neoplastic hepatocyte progenitor cells. In this study, we examine the immunophenotype of the various epithelial cells of hepatoblastoma with special emphasis on the small undifferentiated cell component and compare it with that of adult hepatocytes and hepatic stem (oval) cells. Putative stem cells in the liver can express all of the following markers: alpha-feto protein, CK19 (OV-6), chromogranin A, Bcl-2, HepPar-1, and alpha1 microglobulin. The latter, like alpha-feto protein, is a plasma protein synthesized by hepatocytes. Both alpha1 microglobulin and HepPar-1 are expressed in fetal liver cells as early as 7 weeks of intrauterine life. They are also expressed in hepatocellular carcinoma and in hepatocytic cell lines derived from normal fetal or adult liver. Formalin-fixed, paraffin-embedded archival tissues from 10 predominantly epithelial hepatoblastomas were immunostained with antibodies directed against CD 34, alpha1 microglobulin, Bcl-2, HepPar 1, and CK19 using the avidin-biotin-peroxidase method. The undifferentiated small cell component did not express any of the markers studied, namely, Bcl-2, HepPar-1, alpha(1) microglobulin, CD34, or CK19. Hepatocyte-like cells were alpha1 microglobulin- and HepPar-1-positive, with the intensity of staining correlating with the degree of hepatocytic differentiation. Bcl-2 expression was restricted to areas of ductular differentiation. CK19 was detected in foci that showed duct formation. The small cells of hepatoblastoma did not express HepPar-1, Bcl-2, CK19, alpha1 microglobulin, or CD34, markers that characterize the immunophenotype of hepatic stem cells ("oval" cells). Thus, this observation raises the following questions: (1) is "hepatoblastoma" a misnomer? (2) is the expression of tumor antigens dysregulated in hepatoblastoma? (3) does the liver have two different types of progenitor cells, oval cells and blastemal cells, with differing immunophenotypes? and (4) do the blastemal cells, rather than oval cells, represent the more primitive progenitor cells of the liver?
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PMID:Small cells in hepatoblastoma lack "oval" cell phenotype. 1367 57

CD10 antigen is a 100-kDa-cell surface zinc metalloendopeptidase expressed in a variety of normal and neoplastic lymphoid and nonlymphoid tissues including melanomas. It was recently shown that metastatic melanomas express more CD10 than primary tumors. We evaluated CD10 expression in tumor and stromal cells in 70 biopsies with primary and 28 with metastatic malignant melanomas. Ki-67, Bcl-2, and Bax were also examined to investigate whether CD10 expression is associated with tumor proliferation index or factors of apoptosis. Formalin-fixed/paraffin-embedded tissues were studied by immunohistochemistry. More advanced primary tumors had higher CD10 expression in the tumor cells (r = 0.27, P = 0.03 for Clark levels and r = 0.29, P = 0.02 for Breslow) and higher Ki-67 proliferation fraction (r = 0.32, P = 0.007 for Clark levels and r = 0.32, P = 0.001 for Breslow). Similarly, CD10 expression in the intratumoral stromal cells was also higher in primary tumors with higher Clark level (P = 0.04, linear-by-linear association) and tumor thickness according to Breslow (r = 0.33, P = 0.01). The presence of CD10+ peritumoral stromal cell cuffs was also positively associated with tumor thickness according to Breslow (r = 0.27, P = 0.05). Also, expression of CD10 and Ki-67 were significantly higher in metastatic than in primary tumors (P = 0.01 and 0.02 respectively), but Bcl-2 expression was higher in primary melanomas (P = 0.02). We conclude that CD10 expression in malignant melanoma is associated with tumor progression.
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PMID:CD10 protein expression in tumor and stromal cells of malignant melanoma is associated with tumor progression. 1520 82


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