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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The profiles of functional (proliferative rate and cell distribution in the cell cycle) and phenotypic (nuclear DNA content and hormone receptor status) biological markers and the expression of P53 and Bcl-2 proteins were prospectively evaluated in breast cancers before and after different regimens of primary chemotherapy. Overall, changes induced on the 2 proliferation indices (3H-thymidine labelling index, 3H-dT LI, and flow-cytometric S-phase fraction, FCM-S) mainly consisted of a decrease for rapidly proliferating tumours and an increase or no change for slowly proliferating tumours. However, when considered as a function of treatment type, changes of 3H-dT LI and FCM-S were superimposable in rapidly proliferating tumours, regardless of the type of treatment, and in slowly proliferating tumours only after anthracycline-including regimens. Conversely, following CMF, FCM-S was increased in 90% of the cases and 3H-dT LI in only 50%. Our data imply that the 2 proliferation indices could reflect different phenomena: an actual variation of proliferative activity by 3H-dT LI and an accumulation of cells in the S-phase by FCM-S. In addition, a higher accumulation of cells in G2-M phases could be detected by FCM after anthracycline-including regimens than after CMF. The fraction of P53-positive cells was reduced by primary chemotherapy in about 50% of P53-positive tumours, whereas Bcl-2 expression was only marginally affected. DNA ploidy and hormone receptor status did not change in about 75% of cases, regardless of the chemotherapeutic regimen.
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PMID:Changes in biological markers after primary chemotherapy for breast cancers. 772 38

Non-small-cell lung cancer (NSCLC) prognosis is strictly related to well-established clinicopathological parameters which have unfortunately become insufficient in the prognostic evaluation of this type of cancer. As p53 and bcl-2 gene deregulations are frequently involved in several types of epithelial malignancies, we investigated the Bcl-2 and p53 protein expression in 91 and 101 cases of NSCLC respectively. The expression was then compared with established indicators of prognosis and biological behaviour of the tumours. No relationship was observed between Bcl-2 and either clinicopathological or biological parameters such as histology, grading, tumour status, nodal metastasis and proliferative activity evaluated by scoring proliferating cell nuclear antigen expression and Ki-67 immunoreactivity. However, the mean Bcl-2 expression was significantly lower in patients who developed metastasis during follow-up or died of metastatic disease (P = 0.006 and P = 0.01 respectively). Moreover, survival probability was higher in patients who expressed the Bcl-2 protein (P = 0.0002). In contrast with this, p53 protein accumulation was observed in tumours with metastatic nodal involvement (P = 0.02) or in patients who developed metastasis during follow-up (P = 0.01), although no correlation was found between p53 expression and overall survival. An inverse relationship was also found between Bcl-2 and the anti-oncogene protein product p53 (P = 0.01). Thus, a high proportion of NSCLCs express p53 and Bcl-2 proteins and their expression may have prognostic importance.
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PMID:Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell lung cancer. 773 90

Results from our studies on the clinical applicability of proliferation markers and growth factors in the histopathological assessment of malignancy and prognosis of ovarian neoplasms are presented. Bromodeoxyuridine incorporation, Ki 67 antigen visualization and proliferation cell nuclear antigen expression indicated location and extent of cell proliferation, though not uniformly as compared to flow cytometry and mitotic counting. Clinicopathological correlations of the occurrence of programmed cell death, apoptosis, as indicated by morphology gave inconclusive results, as did analysis of Bcl-2 expression. Increased visualization of p53 protein was associated with increased degree of malignancy but was inconsistent in individual specimens. Growth factor expression, in particular transforming growth factor beta staining intensity, gave additional information on cell behaviour as did vascular endothelial growth factor distribution on vascularization and vessel neoformation when compared to platelet derived growth factor expression, useful in isolated specimens, and to basic fibroblast growth factor expression. The markers presented are indispensible in certain tumour types and give additional information improving our understanding of ovarian neoplasms and tumour classification in general but are mostly not yet reliable enough for clinically applicable conclusions of individual patients.
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PMID:Cell proliferation markers and growth factors in ovarian cancer. 774 6

Adenovirus E1B 19K protein prevents premature death of adenovirus-infected cells. Viral mutants (19K mutants) defective in the 19K protein induce enhanced cell death, resulting in fragmentation of viral and cellular DNA. The 19K protein can also suppress the effects of certain external cell death-inducing stimuli, such as tumor necrosis factor alpha and various DNA-damaging agents that induce apoptosis. We have examined viral infection of permissive human cells and nonpermissive rat cells to determine if the 19K mutant induces apoptotic or necrotic type of cell death. Infection of normal rat kidney cells with an adenovirus type 2 19K deletion mutant induces internucleosomal DNA fragmentation and condensation of nuclear chromatin. Electron microscopic examination of these cells revealed the presence of condensed subnuclear bodies characteristic of apoptosis. In contrast, infection of human A549 cells induces random DNA fragmentation, and these cells do not exhibit characteristic condensation of the nuclear chromatin but contain enlarged nuclei loaded with virus particles. Therefore, it appears that adenovirus infection induces both apoptotic and necrotic types of cell death, depending on the cell type. Both types of cell death can be suppressed by E1B 19K protein. Similarly, a recombinant adenovirus expressing the human Bcl-2 protein but lacking the E1B proteins can efficiently suppress both apoptotic and necrotic cell death induced by adenovirus infection. The requirement of p53 tumor suppressor protein in adenovirus-induced cell death was investigated by infection of human Saos2 and mouse p53 nullizygous (p53-/-) cells lacking p53 tumor suppressor protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:p53-independent apoptotic and necrotic cell deaths induced by adenovirus infection: suppression by E1B 19K and Bcl-2 proteins. 775 71

HHV-6 infected immature T (HSB2) and Hodgkin (HDLM2) cells and biopsy tissues from lymph nodes of patients with Hodgkin's disease (HD) and Kikuchi lymphadenitis (KL) were studied immunohistologically for virus antigen expression and for the oncogene/anti-oncogene products ras, bcl-2 and p53. Cell proliferation and cell death were tentatively monitored in tissue culture by PCNA staining, by viability testing and in situ end labeling of fragmented DNA. PCNA was also used in biopsy samples. KL is characterized by high incidences of focal cell death (i.e. histiocytic necrotizing lymphadenitis), while HD is apparently more a proliferative disease. The techniques used revealed no significant differences in the cellular expression of viral DNA or antigens among cell lines, HD or KL. The HDLM2 cell line with the superior survival after HHV-6 infection showed a significantly lower expression of p53 and PCNA than HSB2 cells. Biopsy samples from patients with KL did not express p53, and ras and PCNA were observed in fewer cells than in HD. Bcl-2, however, was significantly more frequently seen than in HD. The interpretation of the data is difficult; they suggest that there are additional regulatory influences in control of cell proliferation and cell death, such as cytokines and growth factors, which are altered after viral infection. Also, virus-induced cell death probably includes other mechanisms besides apoptosis, such as cell damage caused by oxygen radicals.
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PMID:[Apoptosis and cell proliferation in HHV-6 infections. Regulatory mechanisms of p53/bcl-2/ras interactions]. 776 57

Bcl-2 protein expression has been found to block apoptosis and its overexpression has been implicated in lymphoid malignancies where the chromosomal translocation t(14;18) is present. In this study we investigated bcl-2 transcription and protein expression in cultured cervical carcinoma cell lines and keratinocytes. Western blotting and immunofluorescence microscopy demonstrated bcl-2 expression in the cytoplasm of 4 out of 5 cervical carcinoma cell lines examined (HeLa, CaSki, C-33A, and HT-3, but not SiHa). Bcl-2 protein expression was undetectable in normal keratinocytes. None of the cell lines examined demonstrated chromosomal translocation or rearrangement at the major breakpoint-cluster region (MBR) of the bcl-2 gene using either Southern blot or polymerase chain reaction (PCR) analyses. Northern blot analysis demonstrated low levels of bcl-2 transcription in HeLa, CaSki, and C-33A cell lines while reverse transcriptase (RT)-PCR demonstrated bcl-2 transcription in all cervical carcinoma cell lines which had bcl-2 protein expression. Thus, these data suggest that bcl-2 expression occurs in cervical carcinoma cell lines in the absence of chromosomal translocation or rearrangement of the bcl-2 gene. However, each of these cervical carcinoma cell lines contains inactive p53, either due to mutation (C-33A and HT-3) or via complexation and degradation with human papillomavirus (HPV) 16/18 E6 protein (HeLa and CaSki). Thus, functional p53, which can induce apoptosis in certain cells, is not present in these cervical cells which have increased bcl-2 expression. Increased bcl-2 expression under conditions of p53 inactivation may provide cells with a selective advantage for survival and consequently play a role in the development of cervical carcinogenesis.
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PMID:Bcl-2 protooncogene expression in cervical carcinoma cell lines containing inactive p53. 776 85

The p53 gene located in the short arm of chromosome 17 at position 17p13, is involved in the negative regulation of cellular growth. p53 mutation seems to be the most frequent genetic alteration found in human cancer. Mutant conformation of the p53 gene is associated with cell proliferation and tumour progression, and in most cases implies p53 stabilization, which renders the p53 protein detectable through the use of immunohistochemical techniques. p53 expression is a frequent finding in high grade lymphomas of either B or T cell lineage, having been detected in 30% of cases in our series. The focal presence of p53+ cells was seen in a wide range of low and high grade lymphomas, including lymphadenitis and reactive tonsils. In 37.5% of cases this increased expression of p53 was secondary to mutation in highly conserved regions (exons 5-8). Unlike findings reported in other tumours, in lymphomas, p53 expression seems to be secondary to genetic alterations other than p53 mutation. Initial data suggest that the MDM2 protein could be involved in inactivating p53 protein in most of these cases. Finally, p53 expression has been found to be a poor prognostic marker in high grade B-cell lymphomas in a large series of cases. High p53 expression was associated with a short survival, this relation being stronger in cases with simultaneous bcl2 expression.
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PMID:p53 expression in non-Hodgkin's lymphomas: a marker of p53 inactivation? 777 62

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

When deprived of autocrine growth factors, Epstein-Barr virus (EBV)-immortalized B cells stop growing and die. In this study, we show that death of EBV-immortalized cells deprived of autocrine growth factors occurred by apoptosis. Cycloheximide, a protein synthesis inhibitor, inhibited apoptosis, suggesting that de novo protein synthesis is required. Because p53, Bcl-2, and c-Myc were previously implicated in the induction or prevention of apoptosis in other systems, we assessed their possible involvement here. Unlike normal cells that respond to growth factor deprivation by down-regulating c-Myc expression, EBV-immortalized cells continued to express c-Myc, p53, and Bcl-2 at levels comparable to those measured prior to starvation. Consistent with data demonstrating that c-Myc expression is sufficient to drive quiescent cells into the cell cycle, autocrine growth factor-deprived EBV-immortalized cells did not undergo growth arrest but rather continued to proliferate until death, which occurred randomly throughout the cell cycle. In contrast to EBV-immortalized B cells, normal peripheral blood B cells activated in vitro with anti-CD40 monoclonal antibody and interleukin 4 rapidly down-regulated c-Myc expression and underwent growth arrest in response to growth factors and serum deprivation. These findings demonstrated that c-Myc expression is deregulated in EBV-immortalized cells. Addition of antisense oligonucleotides to c-Myc specifically promoted the survival of starved EBV-immortalized cells and suppressed growth of nonstarved EBV-immortalized cells. Thus, deregulated expression of c-Myc in EBV-immortalized cells promotes proliferation and apoptosis following autocrine growth factor deprivation.
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PMID:A role for deregulated c-Myc expression in apoptosis of Epstein-Barr virus-immortalized B cells. 780 56


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