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)

To evaluate the relationship between cell proliferation and apoptosis in sporadic colorectal carcinogenesis, immunohistochemistry for proliferation-associated antigen Ki-67 and in situ end labelling for identifying apoptotic bodies were performed on paraffin sections from 59 adenomas and 22 carcinomas. These results were correlated with the expression of the proliferation and apoptosis modulators Bcl-2 and p53. Carcinomas showed increased proliferation and apoptosis compared with adenomas (P<0.0001, P<0.001, respectively). There were positive linear correlations between proliferation and apoptosis in adenomas and carcinomas (P<0.02, P<0.05, respectively). The proliferative rate increased significantly from mild to moderate, and from moderate to severe dysplasia (P<0.002, P<0.001, respectively). Apoptotic rate also increased in this sequence, but the increases did not reach statistical significance (both P>0.05). Expression of Bcl-2 was associated with lower apoptotic rate in adenomas (P<0.025) but not in carcinomas (P>0.25), whereas p53 expression was correlated with higher proliferative rate in both adenomas and carcinomas (P<0.01, P<0.05, respectively). An inverse relationship between Bcl-2 and p53 expression was seen in both adenomas and carcinomas (P<0.05, P<0.005, respectively). These data suggest that the normal balance between proliferation and apoptosis is disturbed in colorectal carcinogenesis, both being increased, but proliferation occurs in excess. Bcl-2 and p53 may each play a role in modulating cell apoptosis or proliferation during the development of colorectal carcinoma.
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PMID:Imbalance between proliferation and apoptosis in the development of colorectal carcinoma. 987 Jun 85

Bcl-2 is present in a cytoplasmic distribution in cells that express high levels of this oncoprotein. In contrast, using immunocytochemistry in cells expressing low levels of bcl-2, such as KB human carcinoma cells, we and others have shown that bcl-2 is present on the surface of mitotic chromosomes. However, monoclonal antibodies reactive with an epitope representing amino acids 41-54 of the bcl-2 sequence did not detect bcl-2 in other phases of the cell cycle. This study extended those earlier findings to determine if bcl-2 was expressed as a cyclin or if this pattern was an artifact of immunocytochemistry. Immunofluorescence studies in several other human cell lines showed the same mitotic distribution of bcl-2. Other studies using flow cytometry also showed selective mitotic phase detection of bcl-2. A comparison of available commercial antibodies showed that, in spite of reactivity with denatured bcl-2 on Western blots, clear reactivity with bcl-2 in fixed cells was found only with those reactive with the (a.a. 41-54) epitope. With RNase protection and Western blot analyses, cells synchronized at various stages of the cell cycle showed constant levels of bcl-2 mRNA and protein. Analysis of bcl-2 using Western blots showed a band with the same apparent molecular weight as that seen in comparison with authentic bcl-2 overexpressed in the cytoplasm. The retention of bcl-2 on chromosomes in unfixed, permeabilized preparations was influenced by protease treatment, phosphate, and pH. Studies using isolated chromosomes showed that much of the bcl-2 in these cells was attached to chromosomes in mitosis, had the expected molecular weight, and was phosphorylated in the same manner as that seen in whole-cell extracts. These results show that bcl-2 is not a cyclin and that the bcl-2 localized on chromosomes is the same molecule seen by immunoblotting. These results suggest that the reactive (a.a. 41-54) epitope present in bcl-2 is somehow modified or masked in interphase.
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PMID:Mitotic chromosomal bcl-2. I. Stable expression throughout the cell cycle and association with isolated chromosomes. 988 50

Detection of tumor-associated alterations in peritumoral normal mucosa may give insight into the molecular pathogenesis of oral cancer. In the present study, 100 archival oral squamous cell carcinomaswith adjacent nontumorous mucosa were immunohistochemically investigated with antibodies against p53, Mdm2, Bcl-2, WAF1, MIB1, epidermal growth factor receptor (EGF-R), and various CD44 isoforms. Additionally a standardized argyrophilic nucleolar organizer region (AgNOR)-associated proteins analysis was performed. No correlation was found between p53, Mdm2, Bcl-2, and WAF1 immunophenotypes of the respective tumors and adjacent mucosa. The proliferation-associated markers MIB1 and AgNORs showed a statistically significant sequential increase from normal to dysplastic mucosa to invasive carcinoma. Investigation of various CD44 adhesion molecules revealed a highly variable expression pattern in overt carcinomas with a significantly decreased expression of CD44 v4 and v9 variants and unaltered strong expression of v5 and v6 isoforms compared with normal oral epithelium. We conclude that proliferation markers (MIB1 and AgNORs), as well as selected CD44 isoforms, represent useful markers for the assessment of precancerous lesions. They may be utilized for screening patients at high risk for the development of oral cancer.
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PMID:Immunophenotypic analysis of normal mucosa and squamous cell carcinoma of the oral cavity. 989 90

Epstein-Barr virus (EBV) causes lymphoproliferative diseases in immunocompromised patients and is associated with endemic Burkitt lymphoma, nasopharyngeal carcinoma and some cases of Hodgkin disease. The latent membrane protein 1 (LMP1) of EBV is a transmembrane protein that is essential for the transformation of B lymphocytes. LMP1-mediated up-regulation of Bcl-2 is thought to be an important element in this process. As an approach to explore novel treatments for EBV-associated lymphomas, we constructed a single-chain antibody (sFv) directed against LMP1 to achieve functional inhibition of this oncoprotein in EBV-transformed B lymphocytes. We demonstrated that intracellular expression of an endoplasmic reticulum (ER)-targeted form of this sFv markedly reduced LMP1 protein levels. We also observed a decrease in intracellular level of this protein which correlated with a marked reduction of Bcl-2 expression in EBV-transformed B lymphocytes. We further demonstrated that anti-LMP1 sFv-mediated reduction of Bcl-2 correlated with increased sensitivity of these cells to drug-induced cell death. Therefore, these data suggest that an anti-LMP1 sFv used in combination with conventional chemotherapy may be useful for gene therapy of EBV-associated lymphomas in immunocompromised patients.
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PMID:Phenotypic knock-out of the latent membrane protein 1 of Epstein-Barr virus by an intracellular single-chain antibody. 993 Mar 17

Our previous studies indicate that cadmium in mice can inhibit the formation of chemically induced and spontaneously occurring tumors in the liver and lung. Cadmium is an effective anti-tumor agent when given at non-toxic doses and even when given well after tumor formation, implying a unique sensitivity in certain tumor cells. The present studies tested the ability of cadmium to inhibit growth and progression of transplanted human pulmonary tumor xenografts. Male athymic nude mice were inoculated with either H460 cells, originally derived from a non-small cell pulmonary carcinoma, or DMS 114 cells, originally derived from a small cell lung carcinoma, under the left renal capsule. Starting 1 week later mice received 0, 125 or 250 p.p.m. cadmium in the drinking water, levels without effect on host animal growth or survival, and were observed over the next 4 weeks (H460 cells) or 100 days (DMS 114 cells). An additional experiment gave cadmium as an i.v. loading dose (20 micromol/kg) 4 days after renal inoculation with H460 cells and 200 p.p.m. cadmium in the drinking water from 7 days onward, with an observation period of 28 days. Cadmium caused dose-related reductions in the growth of tumors resulting from the inoculation of either H460 or DMS 114 cells of up to 83%. Additionally, cadmium reduced the rate of tumor metastasis to the lung by up to 58%. Cadmium treatment had no effects on either Bcl-2 or Bax protein expression in tumor xenografts, indicating that apoptotic pathways probably do not contribute to this anti-neoplastic effect. These studies show cadmium can effectively reduce growth and progression of human lung carcinoma xenografts in a fashion that is probably independent of apoptosis.
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PMID:Cadmium-induced inhibition of the growth and metastasis of human lung carcinoma xenografts: role of apoptosis. 993 51

To clarify whether advanced colorectal carcinomas and tumor-neighboring mucosa simultaneously produce both Bcl-2 protein and gut neurohormonal polypeptides and/or amines, and the interrelationship of these phenomenon, we studied retrospective analysis of Bcl-2 protein production and neuroendocrine characteristics in 52 cases of advanced colorectal carcinoma and surrounding mucosa. All of the tumor-neighboring mucosa presented hyperplasia. The rates of enhanced immunoreactivity of the tumor-neighboring mucosa and of positive immunoreactivity of the carcinomas against human Bcl-2 protein and against human vasoactive intestinal polypeptide, pancreatic polypeptide and somatostatin were 78.8% and 94.2%, 82.7% and 59.6%, 78.8% and 67.3%, and 88.5% and 84.6% respectively. Double immunostaining for Bcl-2 protein and each peptide hormone revealed simultaneous expression. In contrast, that of tumor-neighboring mucosa and carcinomas to serotonin and chromogranin-A and to argyrophilia were 11.5% and 1.9%, 32.7% and 17.3%, and 26.9% and 21.2%, respectively. We concluded that tumor-neighboring crypt cells displayed not only hyperplasia but also neuroendocrine characteristics and that enhanced Bcl-2 protein immunoreactivity correlated with tumor occurrence in the wall of the colorectum. The production of Bcl-2 protein by tumor cells and tumor-neighboring crypt cells indicates that the bcl-2 protooncogene may act not only as an inhibitor of apoptosis but also as an inducer of neuroendocrine differentiation from the latent characteristics of the endodermal stem cell.
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PMID:Bcl-2 protein expression and gut neurohormonal polypeptide/amine production in colorectal carcinomas and tumor-neighboring mucosa, which closely correlate to the occurrence of tumor. 998 48

The immunohistochemical expressions of the apoptosis-related proteins Bcl-2, Bcl-xL/S, Bax and Bak were investigated in tumor specimens selected from 58 consecutive patients undergoing surgery for advanced colorectal carcinoma. The expression patterns in 50 specimens of adjacent normal colonic mucosa were also examined. In the normal colonic mucosa, Bcl-2-positive epithelial cells tended to be located at the base of the crypts, while the Bcl-xL/S-, Bax- and Bak-positive epithelial cells tended to be located at the luminal surface. The intracellular expression patterns of Bcl-2 and Bax were diffuse cytoplasmic, whereas those of Bcl-xL/S and Bak were granular cytoplasmic. In the adenocarcinomas, the intracellular expression patterns of all antibodies were diffuse cytoplasmic, and the percentages of Bcl-2-, Bcl-xL/S-, Bax- and Bak-positive cases (>20% of cancer cells labeled) were 29%, 43%, 45% and 69%, respectively. Bax expression was significantly correlated with less lymph vessel invasion (p=0.02) and less depth of invasion (p=0.04). In relation to prognosis (5-year-survival), the patients with Bax-positive tumors had significantly better prognoses than the patients who had Bax-negative tumors (p<0.05). However, the Bcl-2, Bcl-xL/S and Bak expressions were not related to any clinicopathological factors examined. Thus, Bax expression may be an additional prognostic marker in colorectal carcinomas.
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PMID:Prognostic significance of Bcl-2, Bcl-xL/S, Bax and Bak expressions in colorectal carcinomas. 1002 6

Apoptosis is a programmed cell death process in which cells commit suicide under certain environmental conditions. Recent studies suggest that apoptosis is controlled by a variety of cellular genes, and dysregulation of these genes plays an important role in the pathogenesis of human diseases, including cancer. BAG-1 is a novel anti-apoptotic protein isolated by its interaction with another anti-apoptotic protein, Bcl-2. It binds to several hormone receptors and growth factor receptors and modulates their function in apoptosis. However, the role of BAG-1 in the oncogenesis of human cervical cancer has yet to be illustrated. In this study, we examined the expression of BAG-1 in cervical normal and carcinoma cultured cells and tissues. BAG-1 was overexpressed in human cervical carcinoma cell lines and tissues. Overexpression was regulated at the transcriptional level. The increased expression of BAG-1 was correlated with enhanced resistance of cervical carcinoma cells to apoptosis induced by a DNA-damaging reagent. In addition, overexpression of BAG-1 enhanced the resistance of cervical cells to apoptosis. This study provided the first evidence that BAG-1 is upregulated in human cervical cancer and may play an important role in apoptosis and human cervical carcinogenesis.
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PMID:Overexpression of anti-apoptotic gene BAG-1 in human cervical cancer. 1004 62

EAT/mcl-1 showed increased expression during the differentiation of a multipotent human embryonic carcinoma cell line, NCR-G3, and of myeloblastic cells "ML-1," and has sequence similarity to Bcl-2. In this present study, we determined whether the apoptotic cell death induced by chemotherapeutic agents could be inhibited by EAT/mcl-1, as has been found with Bcl-2. Cells transfected with EAT/mcl-1 showed higher resistance to cis-diammine dichloroplatinum (II) (CDDP) and carboplatin compared with the parental line (10)1 and neomycin-resistance gene-transfected clone, (10)1/neo. There was, however, no difference in sensitivity to etoposide, N,N-bis-(2-chloroethyl)-N'-(3-hydroxypropyl) phosphordiamidic acid cyclic ester monohydrate, adriamycin or other chemotherapeutic agents tested. DNA fragmentation of the parental cells following treatment with CDDP and carboplatin was observed in a concentration-dependent manner. In contrast, cells transfected with EAT/mcl-1 did not show DNA fragmentation following treatment with the same concentration of these drugs. EAT/mcl-1 was capable of delaying the onset of p53-independent apoptosis, although it could not inhibit apoptosis completely. Since CDDP and carboplatin damage DNA and then activate c-abl and the JNK/SAPK pathway, EAT/mcl-1 may inhibit p53-independent apoptosis through a c-abl/JNK (SAPK)-dependent mechanism. EAT/mcl-1 has functional homology to Bcl-2 in that it can enhance cell viability under conditions which otherwise cause apoptosis and increase resistance to chemotherapeutic agents.
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PMID:EAT/mcl-1, a member of the bcl-2 related genes, confers resistance to apoptosis induced by cis-diammine dichloroplatinum (II) via a p53-independent pathway. 1008 94

The immunohistochemical expression of bcl-2 protein, and its correlations with clinicopathological features and prognosis were studied in patients with invasive breast carcinoma. Bcl-2 positive expression significantly correlated with hormone receptor positivity and histological tumor differentiation, and inversely correlated with p53 overaccumulation. No correlation was observed between bcl-2 expression and patient age, menopausal status, tumor size, and lymph node metastasis. Survivals of stage I to III patients who had not received adjuvant hormonal therapy showed no difference between bcl-2-positive and -negative tumors, even if patients were divided as with or without adjuvant chemotherapy, or with or without nodal involvement. In consequence, immunohistochemical bcl-2-positivity correlates with positive hormone receptors and well differentiated phenotypes in invasive breast carcinoma, however, it might not predict response to adjuvant chemotherapy and not be a favorable predictive value in patients treated without adjuvant hormonal therapy.
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PMID:Clinical significance of immunohistochemical Bcl-2 expression in invasive breast carcinoma. 1020 94


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