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)

Bcl-2 is a key protein involved in the control of apoptosis. Our previous studies on breast and endometrium indicated hormonal regulation of bcl-2 in these tissues. In the present work we have analyzed Bcl-2 and Bax protein expressions in MCF-7 and T47-D, 2 hormone-dependent breast-cancer cell lines, by immunoblots. Estradiol markedly increased Bcl-2 protein content, both in short- and in long-term treatments of MCF-7 cells. Two types of anti-estrogens (4-hydroxytamoxifen and RU 58668) were able to reverse this effect. Also, a synthetic progestin (ORG 2058) was able to decrease the Bcl-2 level in T47-D cells. The level of Bax protein, however, was not affected in the same conditions of hormonal treatments. The level of Bcl-2 expression was 4.5-fold higher in MCF-7 than in MDA-MB 231 (an estradiol-independent cell line). From these results, we infer the existence of hormonal regulation of Bcl-2 expression and evoke a novel role for estradiol and progestin in the genesis of breast cancer.
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PMID:Antagonism between estradiol and progestin on Bcl-2 expression in breast-cancer cells. 889 51

Bcl-2 and p53 gene products (Bcl-2, p53) are important regulators of apoptosis and cell proliferation, and their immunohistochemical expression may help to identify high-risk breast cancer patients. The authors evaluated p53 and Bcl-2 immunoreactivity in 178 node-negative breast cancers (NNBC) with long-term follow-up (median, 60 months). Bcl-2 was seen in 111 (62%) cases, and was significantly associated with small tumor size, nonductal morphology, low tumor grade, estrogen-receptor (ER) positivity, and p53 negativity. p53 overexpression (ie, > 15% reactive nuclei) was observed in 31 (17%) cases, and was associated with lower age, large tumor size, ductal morphology, high tumor grade, negative ER status, and lack of Bcl-2 immunoreactivity. In univariate analysis, the variables associated with short relapse-free survival (RFS) were large tumor size (P = .002), high histological grade (P = .01), high mitotic count (P = .03), and high Nottingham prognostic index (NPI) (P = .0002). In multivariate analysis (final model), only the NPI was of independent prognostic value concerning RFS.
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PMID:Bcl-2 and p53 expression in node-negative breast carcinoma: a study with long-term follow-up. 891 23

The synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) has been used in breast cancer prevention and treatment. However, the molecular mechanisms mediating the effects of 4-HPR remain elusive. In the present study, we examined the effects of 4-HPR on components of apoptosis pathway (i.e Bcl-2 and Bax) and apoptotic death in both estrogen receptor-positive and estrogen receptor-negative cell lines. We found that: (1) 4-HPR treatment resulted in decreased Bcl-2 mRNA but not Bax mRNA levels; (2) the effect of 4-HPR on Bcl-2 mRNA level was different from other retinoids; (3) 4-HPR treatment induced apoptosis in both estrogen receptor-positive and -negative cells. Hence, the breast cancer chemopreventive properties of 4-HPR may involve modulation of apoptosis pathways.
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PMID:Effect of N-(4-hydroxyphenyl)retinamide on apoptosis in human breast cancer cells. 891 68

We have investigated the ability of several drugs commonly used in the treatment of human cancer to induce bcl2 phosphorylation and cell death in human cell lines derived from acute leukemia, lymphoma, breast cancer, and prostate cancer. The results of this analysis indicate that drugs affecting the integrity of microtubules induce bc12 phosphorylation, whereas anticancer drugs damaging DNA do not. Comparison of the effects of taxol and its analogue, taxotere, indicates that taxotere is capable of inducing bcl2 phosphorylation and apoptotic cell death at 100-fold lower concentrations than taxol. Induction of cancer cell death through phosphorylation of bcl2 thus provides an opportunity not only for more refined targeting of therapeutic drugs but for understanding of an important pathway leading to apoptosis. Phosphorylation of bcl2 in drug-treated cancer cells occurs in G2-M, the phase of the cell cycle in which this class of drugs is active. No induction of bcl2 phosphorylation occurs in chronic lymphocytic leukemia cells that overexpress bcl2 but are blocked at G0-G1. Thus, prevention of polymerization or depolymerization of cellular microtubules by this class of cancer therapeutic drugs causes phosphorylation of bcl2, abrogating the normal antiapoptotic function of bcl2 and initiating the apoptotic program in the cycling cancer cells; these results are consistent with a normal physiological role of bcl2 as "guardian of microtubule integrity."
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PMID:Bcl2 is the guardian of microtubule integrity. 900 May 60

It has been thought that there is a particular balance between interferon and humoral immunity in the specific antiviral activity exerted by these systems. A possible relationship has been observed between some interferon-related proteins and the interferon serum level and a predictive significance can be assigned to MxA protein regarding the progression of some haematological malignancies. Both natural and recombinant interferon have been shown to be effective in the treatment of T-cell cutaneous lymphoma and the myeloma cell expression of Bcl-2 oncoprotein correlates to the response to interferon therapy in multiple myeloma patients. It has been thought that the combined therapy including interferon and cis-retinoic acid might be effective in the therapy of metastatic melanoma and breast cancer, whereas the combination of interferon with other chemotherapeutic agents appears to be effective in the treatment of hepatocellular cancer. It has been confirmed that interferon-alpha is useful in the therapy of chronic hepatitis C and a better knowledge regarding the mechanism of action of beta interferon in the therapy of multiple sclerosis has been acquired. Finally, a remarkable report regards the effectiveness of interferon in the therapy of idiopatic dilated cardiomiopathy.
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PMID:[Clinical use of interferon]. 911 15

This study was undertaken to evaluate our ability to detect multiple molecular markers of prognosis and response to treatment in fine needle aspirates (FNA) from patients with primary breast carcinomas. 147 patients with operable primary breast carcinomas who had been recruited to a randomized trial of primary medical therapy (PMT) versus adjuvant chemoendocrine therapy were analysed. FNAs were taken prior to therapy and from this multiple slides were produced using cytospin cytocentrifugation and stored at -80 degrees C for subsequent immunocytochemical analysis (ICA). ICA was performed for oestrogen receptor (ER), progesterone receptor (PgR), p53, Ki67, and Bcl-2. Part of the aspirate was snap frozen and used for flow cytometric analysis of ploidy and S-phase fraction (SPF). In a subgroup of 50 patients who had surgery prior to systemic therapy, as well as FNAs, sections were also taken from paraffin-embedded blocks and stained by ICA for ER, PgR and p53 for validation. In these patients ER was additionally measured by enzyme immunoassay (EIA) from frozen tissue taken at surgery. ER, PgR, p53, Bcl-2, and Ki67 were successfully detected by ICA while ploidy and SPF were successfully measured by flow cytometry from FNA material. The percentage positive values obtained were reasonable and as follows: 74% for ER, 70% for PgR, 36% for p53, 80% for Bcl-2,68% of tumours were aneuploid and 32% diploid. Significant relationships between these measurements were observed in accordance with expectations. The concordance for ER, PgR, and p53 from FNA when compared to ICA of matching histological sections was 91.5%, 75.5%, and 75% respectively. For ER the concordance between measurement by ICA of cytological and histological samples and by EIA of frozen tissue was 82.5% and 84% respectively. These results indicate that multiple molecular markers can be adequately tested on cytological preparations from primary breast tumours. These markers can be used to determine prognosis and predict response to PMT.
Breast Cancer Res Treat 1997 May
PMID:Cytological evaluation of biological prognostic markers from primary breast carcinomas. 916 79

In this study, we tested the hypothesis that insulin-like growth factor-1 (IGF-1) modulates apoptosis in human breast cancer cells, HBL100, induced by diverse chemotherapeutic drugs. IGF-1 increased cell survival of HBL100 cells treated with 5-fluorouracil (antimetabolite), methotrexate (antimetabolite), tamoxifen (antiestrogen/antiproliferative), or camptothecin (topoisomerase 1 inhibitor) and after serum withdrawal. Elevated cell survival was not due to an increase in cell proliferation by IGF-1, but rather to an inhibition of apoptosis. Evidence for death by apoptosis was supported by cellular morphology and DNA fragmentation. There were no changes observed in Bcl-2 protein or bax mRNA levels. Extracellular matrix (ECM) is known to influence the apoptotic response of cells; therefore, the antiapoptotic effect of IGF-1 on breast cancer cells was examined using different ECMs: laminin, collagen IV, or Matrigel. IGF-1 protected cells from apoptosis induced by methotrexate on all ECMs tested, providing the first evidence that IGF-1 protects against apoptosis in three-dimensional culture systems. These data provide the rationale to search for drugs that lower serum IGF-1 in an effort to improve the efficacy of chemotherapeutic drugs for the treatment of breast cancer.
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PMID:Insulin-like growth factor 1 (IGF-1) alters drug sensitivity of HBL100 human breast cancer cells by inhibition of apoptosis induced by diverse anticancer drugs. 920 78

Ki-S1, a marker of proliferation, and bcl-2, the gene product of which is an antagonist of apoptosis, have been measured in 51 ER-positive primary breast cancers before and during tamoxifen treatment and then related to clinical response. Both markers were detected in the majority of tumours before treatment and, quantitatively, initial expression of Bcl-2 protein, but not Ki-S1, was significantly related to the percentage reduction in tumour volume as assessed by ultrasound. Staining for both markers was lower in post treatment samples than in those taken prior to treatments, but concordant decreases in staining indices were seen in only 11 of the 51 tumours. The results demonstrate, using clinical material, that the response to tamoxifen may involve changes in proliferation and/or susceptibility to cell-death.
Breast Cancer Res Treat 1997 Jun
PMID:The expression of Ki-S1 and BCL-2 and the response to primary tamoxifen therapy in elderly patients with breast cancer. 923 71

In this immunohistochemical study we investigated the expression of Bcl-2 and Bax apoptosis related proteins in node-negative breast carcinomas. The results were correlated with the recurrence rate of the patients. In order to avoid the influence of the most important tumor prognostic parameters we selected two groups of node negative breast ductal carcinomas that were grade II according to Bloom and Richardson classification, had a diameter of 1-3 cm but differed in clinical outcome: 44 of the patients had a 10 year disease-free survival while 46 developed metastatic disease in the same period of time. Bcl-2 and to a lesser degree Bax expression were inversely related with distant metastases (Pbcl-2 = 0.007, Pbax = 0.03). Combined analysis of Bax/Bcl-2 expression in relation to clinical outcome showed that the absence of both factors was more strongly associated with the development of distant metastases (P = 0.006, Ptrend = 0.001). Our findings indicate that Bcl-2 and Bax apoptosis-related proteins are good indicators of prognosis in node-negative breast cancer patients, and their combined absence, suggestive of serious deregulation of the apoptotic process, may contribute to the biologic aggressiveness of the tumors.
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PMID:Prognostic significance of apoptosis related proteins Bcl-2 and Bax in node-negative breast cancer patients. 925 70

The biologically active form of vitamin D3, the nuclear hormone 1 alpha,25-dihydroxyvitamin D3 (VD), is an important regulator of cellular growth, differentiation, and death. The hormone mediates its action through the activation of the transcription factor VDR, which is a member of the superfamily of nuclear receptors. In most cases the ligand-activated VDR is found in complex with the retinoid X receptor (RXR) and stimulates gene transcription mainly from VD response elements (VDREs) that are formed by two hexameric core binding motifs and are arranged either as a direct repeat spaced by three nucleotides (DR3) or as an inverted palindrome spaced by nine nucleotides (1P9). The two VD analogues CB1093 and EB1089 are both very potent inhibitors of the proliferation of MCF-7 cultured breast cancer cells displaying approximately 100-fold lower IC50 values (0.1 nM) than the natural hormone. In addition, CB1093 is even more potent in vivo than EB1089 in producing regression of experimental mammary tumors. Moreover, both VD analogues induce apoptosis in MCF-7 cells, but CB1093 is effective at concentrations approximately 10-fold lower than EB1089. In accordance, the reduction of Bcl-2 protein expression showed CB1093 to be more potent than EB1089. This suggests that the antiproliferative effect of CB1093 may be related mainly to its apoptosis inducing effect, whereas EB1089 may preferentially have effects on growth arrest. EB1089 is known to result in a selectivity for the activation of IP9-type VDREs, whereas CB1093 shows a preference for the activation of DR3-type VDREs. This promoter selectivity suggests that the effects of VD and its analogues on growth arrest and the induction of apoptosis may be mediated by different primary VD responding genes. In conclusion, CB1093 was found to be a potent inhibitor of rat mammary tumor growth in vivo. CB1093 also displayed a high potency in vitro in the induction of apoptosis, a process that may be linked to a promoter selectivity for DR3-type VDREs.
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PMID:Sensitive induction of apoptosis in breast cancer cells by a novel 1,25-dihydroxyvitamin D3 analogue shows relation to promoter selectivity. 928 33


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