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)

Neoplasia can be defined as deregulated tissue homeostasis caused by an imbalance between proliferation and apoptosis. Many genes are involved in the maintenance of tissue homeostasis, eg, the c-myc oncoprotein, which is an important regulator of cell proliferation and Bcl-2 protein, which is involved in the regulation of apoptosis. We studied retrospectively indices of proliferation, such as mitotic count and the Mib-1 index, on 51 uveal melanomas and compared their prognostic significance with established indicators of prognosis such as cell type and tumor size. Along the same line we investigated the expression of the regulating proteins c-myc and Bcl-2. Of all parameters tested, the largest tumor diameter and mitotic count were most strongly associated with tumor-related death (P < 0.001 and P = 0.005, respectively). In addition, cell type, the presence of epithelioid cells, the Mib-1 index, and the percentage of cytoplasmic c-myc-positive cells were significant predictive factors. Multivariate analysis showed that the Mib-1 index, largest tumor diameter, and the percentage of cytoplasmic c-myc-positive cells were independent prognostic parameters. Bcl-2 expression did not correlate with clinical outcome. The Mib-1 index correlated with the presence of epithelioid cells (P < 0.03) and the presence of apoptotic bodies (P < 0.001) and c-myc. A strong inverse relationship was found between (nuclear and cytoplasmic) c-myc and Bcl-2 (P < 0.00004 and P < 0.006, respectively), suggesting that Bcl-2 cooperates with c-myc to immortalize uveal melanoma cells.
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PMID:Immunohistochemical and prognostic analysis of apoptosis and proliferation in uveal melanoma. 757 54

Mechanisms of etoposide (VP-16) resistance have been evaluated in a human promyelocytic leukemia HL60 cell line. HL60 resistant (HL60/AR) cells were selected for resistance with adriamycin and were 250-fold resistant to VP-16. We have found that while a significantly higher (10 to 15-fold more) dose of VP-16 was required to induce similar amounts of SDS-KCI-precipitable DNA-protein complex formation in the resistant cell line, there was no difference in the repair of VP-16-induced DNA damage, indicating that differential DNA repair was not involved in VP-16 resistance in HL60 cells. VP-16 treatment significantly inhibited c-myc expression and induced c-jun and c-fos expressions in sensitive cells. In contrast, VP-16 had no effect on c-myc, c-jun or c-fos expressions in resistant cells. The level of bcl2 oncogene was similar in both cell lines; however, treatment with VP-16 resulted in a time- and dose-dependent degradation of the genomic DNA into oligo-sized DNA only in the sensitive cells, indicating that differential expressions of oncogenes (c-myc, c-jun, and c-fos) and susceptibility to apoptosis may play important roles in the sensitivity and resistance to VP-16 in HL60 cells.
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PMID:Differential oncogene expression and susceptibility to apoptosis in the human leukemia HL60 cell lines: implications for etoposide resistance. 764 49

Expression of c-myc and macromolecular synthesis have been associated with physiological cell death. We have studied their requirement for the death of factor (interleukin-3)-dependent cells (FDC-P1) bearing an inducible bcl-2 expression construct. FDC-P1 cells expressing bcl-2 turned off expression of c-myc when deprived of interleukin-3 but remained viable as long as bcl-2 was maintained. A subsequent decline in Bcl-2 allowed the cells to undergo apoptosis directly from G0, in the absence of detectable c-myc expression. Thus c-myc expression may lead to apoptosis in some cases but is not directly involved in the mechanism of physiological cell death that can be controlled by Bcl-2. The macromolecular synthesis inhibitors actinomycin D and cycloheximide triggered rapid cell death of FDC-P1 cells in the presence of interleukin-3, but the cells could be protected by Bcl-2. Thus, the cell death machinery can exist in a quiescent state and can be activated by mechanisms that do not require synthesis of RNA or protein.
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PMID:Neither macromolecular synthesis nor myc is required for cell death via the mechanism that can be controlled by Bcl-2. 769 34

We have established three lymphoma cell lines, HF-1 from one follicular lymphoma (FL) patient, and HF-4 and HF-9 from another. All cell lines carry the characteristic t(14;18) chromosomal translocation and express constitutively the bcl-2 gene product (Bcl-2 protein). Cross-linking of their surface membrane Igs (sIgs) with relevant antibodies triggers a vigorous calcium signal in all three lines but only HF-1 is induced to apoptosis. Treatment with anti-Ig arrests the proliferation of HF-1 within 6-12 h, nucleosomal DNA fragmentation is evident in 18 h and a morphologically complete apoptosis is seen in 24-48 h. While bcl-2 was expressed at equal levels in all lines, the apoptosis-sensitive HF-1 line displayed a much lower expression of c-myc than seen in the apoptosis-resistant line. This finding challenges the concept that expression of bcl-2 per se renders resistance to apoptosis but that the balance between the expression of bcl-2 and c-myc may dictate the outcome of sIg cross-linking. HF-1 is a unique, phenotypically mature human B cell line expressing surface IgG. This cell line offers a new tool for investigations on apoptosis and induction of tolerance in mature B lymphocytes. Our results suggest that some FLs may be amenable to anti-cancer treatment based on anti-sIg antibody induced apoptosis.
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PMID:Cross-linking of surface IgG induces apoptosis in a bcl-2 expressing human follicular lymphoma line of mature B cell phenotype. 769 2

Cells undergo apoptosis in response to a wide range of stimuli, and this response may represent an ancient defence mechanism against pathogens. Bcl-2 is able to prevent apoptosis in many cases. Although blocking cell suicide is not directly oncogenic, enforced bcl-2 expression can lead to cancer by lengthening the life-span of cells, during which time secondary changes, such as activation of additional oncogenes like c-myc, can occur. Bcl-2 cannot block apoptosis of target cells by cytotoxic T lymphocytes. Thus cytotoxic T cells are able to fight viruses that carry anti-apoptosis genes that resemble bcl-2. Genes involved in the regulation of mammalian apoptosis are similar to those that mediate programmed cell death in C. elegans. By studying cell death genes in viruses and worms as well as mammals, we will learn more about this fascinating process.
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PMID:Analysis of the role of bcl-2 in apoptosis. 769 91

The expression of retinoblastoma (Rb), c-Myc and Bcl-2 proteins was studied by immunohistochemical methods in 104 cases of renal adenocarcinoma. One tumour was completely negative for Rb protein and altered expression pattern was detected in 36% of cases. A low fraction of Rb-positive nuclei was related to high grade (P = 0.016) and high mitotic index (P = 0.012). Twenty-eight per cent of the tumours expressed c-Myc in cancer cell nuclei and 87% showed cytoplasmic positivity. Cytoplasmic expression of c-Myc was related to high grade (P = 0.002), while nuclear expression of c-Myc was related to small tumour diameter (P = 0.034), low T category (P = 0.04), low mitotic index (P = 0.019) and expression of c-ErbB-2 (P = 0.0007). Overexpression of c-myc predicted favourable outcome in M0 tumours (P = 0.0157). Bcl-2 was expressed in 20% of tumours and it was related to small tumour size (P < 0.0001), low T category (P < 0.0001), lack of venous invasion (P = 0.008), node negativity (P = 0.015) and absence of metastasis (P = 0.017). In multivariate analysis the expression of Rb, Bcl-2 and c-Myc had no independent prognostic value over T category (P < 0.001), mitotic index (P = 0.008) and combined nuclear grade (P = 0.056).
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PMID:Expression of tumour-suppressor gene Rb, apoptosis-suppressing protein Bcl-2 and c-Myc have no independent prognostic value in renal adenocarcinoma. 771 Sep 55

The reversibility of a differentiation program termed dedifferentiation, redifferentiation, or retrodifferentiation opens a spectrum of new possibilities for cellular development. During differentiation and retrodifferentiation, the expression of gene products associated with a differentiated phenotype and cell cycle regulation demonstrate inverse patterns. This effect requires a coordinated network that simultaneously controls cell growth and differentiation. In particular, crosstalk between induction of differentiation and G0/G1 cell cycle exit can be initiated and sustained by activated serine/threonine kinases and tyrosine kinases. Phosphorylation signals are relayed to certain genes or transcription factors such as Fos/Jun, EGR-1, NF-kappa B, MyoD, or the Myc/Max gene family. However, the precise regulation of these transcription factors to confer signals to differentiation-associated and cell cycle-regulatory genes remains unclear. Cell cycle exit into a transient G0'-arrest cycle or a terminal G0 phase is determined by a network of phosphorylation signals involving the retinoblastoma protein and a variety of factors such as the E2F family, cyclins, and cyclin-dependent kinases. In this context, a variety of differentiation-induced cell lines, including monocytic, neuronal, or muscle cells, can progress through the G0'-arrest cycle, whereby a certain population retains the capacity to retrodifferentiate and reenter the cell cycle. In contrast, the rest of the differentiated population enters the irreversible G0 phase (terminal commitment) that finally results in programmed cell death. The expression of growth arrest-specific (gas and gadd) genes is associated with the G0'-arrest cycle, and other factors, including c-myc, p53, mdm2, and bcl2/bclx, contribute to the regulation of the cell death program. Although the precise signaling cascade determining retrodifferentiation or cell death remains unclear, a coordinated inter- and intracellular regulation could establish a certain biological balance between these exclusive pathways. Consequently, a retrodifferentiation process may provide a potential for cell type conversion or transdifferentiation, whereby retrodifferentiated cells can be induced to develop via a different pathway according to tissue-specific requirements.
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PMID:Retrodifferentiation and cell death. 771 Nov 13

Two interleukin-2 receptor-dependent signaling pathways have thus far been identified: the c-fos/c-jun induction pathway mediated by src family protein-tyrosine kinases and the c-myc induction pathway. Here, we provide evidence for the existence of a third, rapamycin-sensitive pathway, which results in the induction of another proto-oncogene, bcl-2. In the hematopoietic cell line BAF-B03, the expression of any two of lckF505 (an active form of p56lck), Bcl-2, or c-Myc is sufficient to promote transit of the cell cycle, regardless of the activation state of the third pathway. We also provide evidence that epidermal growth factor receptor signaling may act through the same pathway that involves p56lck. These studies demonstrate a novel approach to dissecting signaling pathways regulating cellular proliferation.
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PMID:Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation. 773 74

BCR-ABL is a chimeric oncogene generated by translocation of sequences from the c-abl protein-tyrosine kinase gene on chromosome 9 into the BCR gene on chromosome 22. Alternative chimeric proteins, p210BCR-ABL and p190BCR-ABL, are produced that are characteristic of chronic myelogenous leukemia and acute lymphoblastic leukemia, respectively. Their role in the etiology of human leukemia remains to be defined. Transformed murine hematopoietic cells can be used as a model of BCR-ABL function since these cells can be made growth factor independent and tumorigenic by the action of the BCR-ABL oncogene. We show that the BCR-ABL oncogenes prevent apoptotic death in these cells by inducing a Bcl-2 expression pathway. Furthermore, BCR-ABL-expressing cells revert to factor dependence and nontumorigenicity after Bcl-2 expression is suppressed. These results help to explain the ability of BCR-ABL oncogenes to synergize with c-myc in cell transformation.
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PMID:Tumorigenic activity of the BCR-ABL oncogenes is mediated by BCL2. 777 99

Major differences in the long-term clinical response to castration therapy of prostatic carcinoma suggests intertumoral differences in cellular response and defines a need for identification of patients with an eventually positive outcome as well as those in need of additional treatment. Using morphometry, monoclonal antibodies against Bcl-2, c-myc, Ki-67, and p53 proteins, and an in situ method to visualize apoptotic cells, we examined the short-term response of prostatic tumors to castration in core biopsies from 18 prostatic cancer patients taken the day before and 7 days after castration. At the histological level, 3 tumors seemed practically unaffected by castration. In 15 tumors, castration induced vacuolization of tumor cell cytoplasm and decreases in nuclear area and Ki-67 index. In these 15 tumors, apoptotic index was significantly increased in 6, principally unaffected in 6, and decreased in 3. The 6 tumors responding with an increase in apoptotic index were WHO grade 1 or 2 and negative for p53, c-myc, and Bcl-2 or contained only few Bcl-2- or c-myc-positive tumor cells before therapy. The 12 tumors in which apoptotic index was unaffected or decreased were WHO grade 2 or 3 and immunopositive for one or more of p53, Bcl-2, and c-myc proteins before therapy. The Bcl-2 index was significantly increased in 10 patients. Prostatic tumors may respond in a variety of possibly predictable ways to castration therapy including a decrease in apoptotic index. The magnitude of these responses are not correlated in individual tumors, suggesting that the common classification of prostatic tumors as either androgen dependent (dying after castration) or independent (not responding at all to castration) may be an oversimplification.
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PMID:Castration therapy rapidly induces apoptosis in a minority and decreases cell proliferation in a majority of human prostatic tumors. 777 76


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