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, programmed cell death, was immunohistochemically determined in 55 samples of oesophageal squamous cell carcinoma using the BM1 Mab. Sections from patients not treated (group 1, n = 12) or preoperatively treated by chemotherapy (group 2, n = 11), radiation (group 3, n = 13) or both (group 4, n = 8), and 11 additional cases of high-grade dysplasia or early cancer were examined. Most of the apoptotic cells were BM1-positive and checked by TUNEL proved to be nick end positive. They accounted for 7 (11%), 19 (29%), 21 (32%) and 26 (38%) cells per field in those 4 groups respectively. Chemotherapy and/or radiation significantly increased the number of apoptotic cells as compared to controls (p = 0.029 and p = 0.029, respectively). To assess the implications of the oncogene expression in the apoptotic pathway, additional section stained with bcl2 and p53 were negative for bcl2 and were positive for p53 in 16 samples (37%). Overall, positive cases for p53 mutation showed a significantly decreased incidence of apoptotic cells (p = 0.03). These results suggest that in situ assessment of apoptotic response better correlates to the apoptosis induced by radiation than that by chemotherapy, that abnormalities of the p53 protein decrease the apoptotic response in oesophageal carcinoma, and that immunohistochemical analysis of p53 protein helps to determine the sensitivity to these anticancer agents.
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PMID:Assessment of apoptosis in oesophageal carcinoma preoperatively treated by chemotherapy and radiotherapy. 753 43

Basal cell carcinoma (BCC) is typically a slow-growing malignant tumour, composed of cells similar to those in the basal area of the epidermis. We investigated the expression of bcl-2 (B-cell leukaemia/lymphoma-2) in BCC, and also in squamous cell carcinoma (SCC) of the skin. The proto-oncogene bcl-2 encodes a protein which inhibits programmed cell death (apoptosis). The protein is expressed in basal cells in normal human epithelium, but not in the suprabasal cell layers. Immunohistochemical localization using a monoclonal anti-Bcl-2 antibody revealed bcl-2 expression in all the BCCs (15 patients). SCCs did not express bcl-2 (five patients). The positive Bcl-2 staining of BCC tumour cells supports the hypothesis that BCCs originate from the basal layer of the epidermis. The bcl-2 expression of BCC tumour cells also suggests a neoplastic transformation caused by extended cell survival rather than increased cell proliferation. This type of neoplastic growth is possibly associated with less aggressive tumour behaviour.
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PMID:Expression of the apoptosis-suppressing protein Bcl-2 in non-melanoma skin cancer. 777 78

Epstein-Barr virus (EBV) is associated with tumours of both lymphoid and epithelial origin. Whilst a role for EBV latent genes in the development of these malignancies is accepted, it is also possible that viral proteins involved in EBV replication may influence the oncogenic process. BHRF1 is an immediate early protein which has homology with the Bcl-2 oncogene and can protect B cells from apoptosis. In vivo this protein is most abundantly expressed in the upper layers of oral 'hairy' leukoplakia (HL), a benign hyperparakeratotic tongue lesion which represents a focus EBV replication. We have transfected BHRF1 into the human squamous cell carcinoma line SCC12F which retains several features of normal keratinocytes behaviour in vitro. BHRF1 expression in these epithelial cells is associated with a delay in the commitment of cells to terminal differentiation, increased resistance to the DNA damaging drug, cis-platin and enhanced survival under conditions of serum deprivation. As the differentiation of epithelial cells is an apoptotic process, this data strongly suggests that BHRF1 expression delays the terminal differentiation of epithelial cells through the prevention of apoptosis. This effect of BHRF1, which may normally function to promote productive EBV infection, could contribute to the development of EBV-associated tumours.
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PMID:BHRF1, a viral homologue of the Bcl-2 oncogene, disturbs epithelial cell differentiation. 782 80

In our laboratory, we observed that a case of small cell carcinoma of the lung (SCLC) stained with a monoclonal antibody (Dako Corp., Bcl-2-124) against the Bcl-2 protein. To determine how common this reaction was, and whether it was specific for SCLC, we stained formalin-fixed, paraffin-embedded tissues from 23 cases of SCLC and 20 cases of squamous cell carcinoma of the lung for Bcl-2. Fifteen of the 23 SCLC cases stained positively for the Bcl-2 oncogene protein. In contrast, weak staining was observed in only three of the squamous cell carcinomas (chi 2-test; P = 0.001). In addition, four small cell carcinoma cell lines (H69, H146, H209, and WB) were tested by immunohistochemistry and flow cytometry for expression of this protein; all four were positive. In these and three other (H128, H432, and H510) SCLC lines, Northern blots of polyadenylated RNA revealed expression of the 6-kb Bcl-2 mRNA. Moreover, Western blots of extracts from these cell lines revealed the characteristic 26-kd band for Bcl-2 protein. In a single cell line, H82, which has previously been characterized as a variant SCLC, we failed to detect expression of the Bcl-2-specific mRNA and protein. We therefore conclude that most cases of SCLC of the lung express the Bcl-2 oncoprotein, which could play a role in the pathogenesis of this disease.
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PMID:Small cell carcinomas of the lung express the Bcl-2 protein. 797 36

Mutation, deactivation and disregulated expression of oncogenes and tumour-suppressor genes may be involved in the pathogenesis of oral squamous cell carcinoma (SCC). Deactivation of the p53 tumour-suppressor gene allows cell proliferation and blocks apoptosis of malignant oral keratinocytes. Mutation in the ras oncogene results in persistent mitogenic signalling. Upregulatioed c-Myc expression, in the presence of growth factors, provides an additional proliferative signal. Loss of retinoblastoma tumour-suppressor gene (Rb) function may contribute to oral keratinocyte hyperproliferation and recent evidence suggests that simultaneous deactivation of both p53 and Rb is required for tumourigenesis. Enhanced Bcl-2 and reduced Fas expression inhibit tumour cell apoptosis and may convey resistance to cytotoxic drugs and T cell-mediated cytotoxicity, respectively. Exogenous mutagens such as tobacco, alcohol and viral oncogenes may cause altered expression of oncogenes and tumour-suppressor genes in some cases of oral SCC. The impact of these mechanisms on future therapies for oral SCC is highlighted.
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PMID:Review article: The role of oncogenes, tumour suppressor genes and growth factors in oral squamous cell carcinoma: a case of apoptosis versus proliferation. 870 24

The aim of this study was to investigate bcl-2 expression in head and neck cancer patients and to investigate its correlation with biological and clinical characteristics and outcome of accelerated radiotherapy. A series of 93 patients with squamous cell carcinoma of the head and neck who had been uniformly treated with continuous hyperfractionated accelerated radiation treatment (CHART) were investigated. These patients had also been injected with bromodeoxyuridine (BrdUrd) to measure cell kinetic parameters using flow cytometry (FCM) and their p53 protein status had also previously been described. Bcl-2 expression was assessed using immunohistochemistry. Sixteen of the 93 (17.2%) patients stained positively for bcl-2 proto-oncogene. The percentage of positive tumour cells within the specimens was highly variable, ranging from a few percent to complete positivity. Bcl-2 positivity was correlated with improved local control (p > 0.0016) and survival (p > 0.012) in comparison with non-expressing tumours. There was no correlation between bcl-2 expression and histological grade, T stage or site but overexpressors were almost exclusively node negative. The significance of bcl-2 was reduced when node negative tumours were analysed alone. There was no correlation of bcl-2 with p53 expression but there was a trend for overexpression to be associated with diploidy and rapidly proliferating tumours. These data suggest that bcl-2 expression in head and neck cancer is not associated with disease progression.
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PMID:Bcl-2 expression correlates with favourable outcome in head and neck cancer treated by accelerated radiotherapy. 881 42

In situ hybridization using EBERs and BHLF oligonucleotide probes and immunohistochemistry using monoclonal antibodies against LMP1, EBNA2, BZLF1 protein, p53 protein and bcl-2 protein were performed on 56 primary nasopharyngeal carcinomas. EBERs was detected in 46 cases (82%), and LMP in 17 cases (30%), but EBNA2 was not detected. While 30 of 32 cases (94%) in differentiated non-keratinizing carcinoma (NKC) and 16 of 17 cases (94%) in undifferentiated carcinoma (UNPC) showed EBERs, neither 5 cases of squamous cell carcinoma (SCC) nor 2 cases of adenocarcinoma showed EBERs. This finding confirms latent infection of EBV, especially phenotypical latency II, in NKC and UNPC but not in SCC. Bcl-2 protein was positive in 50 cases (89%), but its expression did not depend on expression of LMP1, which did not demonstrate induction of bcl-2 by LMP1 as seen in vitro. Cytoplasmic BZLF1 expression was detected in 18 cases (32%) whereas BHLF was positive only in 6 cases (11%). This suggests dysfunction of BZLF1, which disrupts viral latency despite its expression. p53 protein was positive in 31 cases (55%), and there was a distinct correlation between expression of BZLF1 and p53 protein (p < 0.001). This suggests that the interaction between BZLF1 protein and p53 protein, which inactivate each other, is one of the tumorigenic factors in NPC.
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PMID:[Interaction between Epstein-Barr virus (EBV) gene expression and antibodies to EBV in nasopharyngeal carcinomas]. 891 Oct 67

This study was conducted to determine whether Bcl-2 overexpression in localized squamous cell carcinoma of the head and neck (SCCHN) might serve as a marker for tumors unlikely to respond to standard treatment. Tissue samples from 33 patients undergoing surgery or irradiation for early-stage SCCHN during the year 1977 to 1992 were stained for Bcl-2. All patients had either T1N0 lesions of the oral cavity, pharynx, or larynx or T1N0 or T2N0 lesions of the true vocal cords. Of the 33 patients, 26 remained disease-free after at least 3 years of follow-up; the remaining 7 patients developed either tumor recurrence or a second primary tumor, 4 of which were fatal. Twelve patients had tissue specimens staining positive for Bcl-2; 6 of these patients had a poor outcome, and 6 had a good outcome. The relationship between poor outcome and overexpression of Bcl-2 in tumor cells was statistically significant (p = .0047 by Fisher's exact test). For tumors overexpressing Bcl-2, there was no significant difference in recurrence rate between those undergoing surgery and those undergoing radiotherapy as the primary mode of treatment. The overexpression of Bcl-2 in early lesions in this study predicted a cure rate of 50%, as opposed to the generally expected 90%, suggesting that Bcl-2 is a significant prognostic indicator in early SCCHN. Future studies will determine if altering the treatment will improve outcome in these patients.
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PMID:Prognostic significance of Bcl-2 expression in localized squamous cell carcinoma of the head and neck. 919 1

The bcl-2 oncogene was originally found in the translocation in a pre-B cell acute lymphocytic leukemia cell line. Since then a high expression of Bcl-2 has been found in many types of cancer. The bcl-2 gene encodes an intracellular membrane-associated protein. Overexpression of bcl-2 inhibits apoptosis induced by many drugs and radiation. In this study the bcl-2 gene status of 9 human head and neck squamous cell carcinoma cell lines was studied. Mutations of the bcl-2 gene were studied at mRNA and DNA levels. The presence and abundance of the Bcl-2 protein in cells were also investigated. In earlier studies the p53 tumour suppressor gene was screened for point mutations, and the radiosensitivity of these cell lines was measured. We were able to amplify bcl-2 cDNA from 5 of the 9 cell lines, which shows that bcl-2 was expressed in these cells. No point mutations were found in the bcl-2 gene in any of these cell lines. Loss of heterozygosity was observed in 2 cell lines at the bcl-2 locus, and these cell lines had no detectable levels of bcl-2 mRNA or Bcl-2 protein. The Bcl-2 protein was abundant in the cell lines with the wild-type p53 gene, and these cell lines were radioresistant. The Bcl-2 protein was also found in many other cell lines in mitotic cells. It seems that cells expressing bcl-2 are radioresistant, and even functional p53 cannot induce apoptosis in these cells.
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PMID:The bcl-2 gene status of human head and neck cancer cell lines. 928 19

Samples of normal esophageal squamous epithelium (n = 10), severe squamous cell dysplasia (n = 22), carcinoma in situ (n = 15), invasive squamous cell carcinoma (n = 172), lymph-node metastasis (n = 21) and 2 permanent esophageal squamous cell carcinoma cell lines were analyzed immunohistochemically for Bax expression using a polyclonal anti-Bax antibody. Immunostaining was evaluated according to a score system (0-8 points) based on the percentage of positive tumor cells and the relative immunostaining intensity. Cytoplasmatic staining for Bax protein was found uniformly in all cell layers of the normal esophageal squamous epithelium. In contrast, a gradual loss of immunoreactivity for Bax was found in a fraction of pre-neoplastic and neoplastic lesions. Upon comparison of the amount of Bax expression between the different types of lesion, however, no significant differences were found between severe squamous cell dysplasias, carcinomas in situ, invasive carcinomas and lymph-node metastases. In both esophageal carcinoma cell lines, immunoreactivity for Bax was found and confirmed by means of Northern blot analysis. In invasive carcinomas, Bax immunoreactivity was inversely correlated with Bcl-2 expression (p = 0.0243) and decreased continuously with decreasing tumor differentiation (p = 0.0011). No correlation was found between Bax expression and the following parameters: depth of invasion, nodal status and tumor size. Bax expression had no influence on the post-operative survival of esophageal cancer patients.
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PMID:Expression of Bax, a pro-apoptotic member of the Bcl-2 family, in esophageal squamous cell carcinoma. 938 64


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