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 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

Cervical cancer is the most common cancer among women in South India. More than 70% of the cases present in stage IIB and IIIB and of these more than 50% fail conventional treatment. The purpose of the present study was to determine the prognostic significance of Bcl-2 and p53 expression in squamous cell carcinomas of the cervix. Using immunohistochemistry, 40 cases of stage IIB and IIIB squamous cell carcinomas of the cervix treated with radiotherapy were studied for the expression of Bcl-2 and p53 protein and their prognostic value ascertained. Bcl-2 was expressed in 65% (n=26) of the tumours. There was a statistically significant association (p=<0.025) between Bcl-2 expression and poorer DFS and OS in stage IIB cases. In stage IIIB, these associations were not obvious probably due to additional genetic events overshadowing the significance of Bcl-2 expression. Only 4/40 (10%) of the cases were positive for p53 protein expression and there was an inverse correlation between p53 expression and Bcl-2 expression. This study suggests that Bcl-2 can be a useful marker to identify the poor prognostic group in stage IIB cases and needs to be confirmed in a larger series.
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PMID:Prognostic significance of Bcl-2 and p53 protein expression in stage IIB and IIIB squamous cell carcinoma of the cervix. 1021 40

To investigate the role of the apoptosis-related genes, Bcl-2, Bax and Survivin genes were analyzed. For the Bax gene, abnormality was detected in 1 of 7 cervical and 1 of 6 endometrial cancer cell lines, 1 of 25 cervical cancer tissues and none of 17 endometrial cancer tissues using PCR-SSCP. In 4 cervical and 2 endometrial cancer cell lines, the ratio of Bcl-2 to Bax expression was higher than the control ratio using Western blotting. Survivin mRNA was detectable in all cell lines and all cancer tissues. The data suggested that these apoptosis-related genes may play important roles in the pathway of carcinogenesis of human uterine cancer.
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PMID:Analysis of Bcl-2, Bax and Survivin genes in uterine cancer. 1037 6

The aim of this study was to provide some insights into the molecular mechanisms involved in p53-dependent apoptosis and growth arrest. Changes in the levels of p53 protein and proteins regulated by p53 were studied in relation to events of the cell cycle and apoptosis in cervical cancer cell lines upon transfection with a p53 expressing adenovirus (Ad5-p53). The post-transfection level of p53 protein in SiHa cells was found to be unchanged during the 24-48 h period. In contrast, the level of p21WAF1 protein was shown to increase to its highest level at 24 h, and decreased gradually up to 48 h after the Ad5-p53 transfection. We further noted that the increase of p21WAF1 was accompanied by G1 arrest at 24 h and the decrease of p21WAF1 was associated with apoptosis at 36-48 h after transfection. An anti-p21WAF1 antibody cross-reactive protein band of approximately 14 kDa was observed in HeLa and C-33A cells when these cells were committed to apoptosis upon Ad5-p53 transfection. In SiHa cells, phosphorylation of pRb was inhibited during the early stage of Ad5-p53 transfection. This was followed by the cleavage of pRb. However, Ad5-p53 transfection did not change the levels of Bax and Bcl-2 proteins. Our results suggested that, Bax and Bcl-2 may not be important for the apoptosis of these cells, whereas cleavage of Rb, and the decrease of p21WAF1 could play important roles in p53-dependent apoptosis.
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PMID:Changes in p21WAF1, pRb, Mdm-2, Bax and Bcl-2 expression in cervical cancer cell lines transfected with a p53 expressing adenovirus. 1074 Dec 85

We investigated the proportion of apoptotic cells and the expression of apoptosis-associated proteins after the delivery of the first week of irradiation for stage IIIb uterine cervical cancer. Thirty patients with stage IIIb squamous cell carcinoma of the uterine cervix who received only irradiation therapy were registered in this study. Specimens were obtained before irradiation therapy and at the end of the first week of irradiation. The apoptotic index (AI) of each tissue specimen was calculated by counting the apoptotic cells and expressed as a percentage. Immunohistochemical evaluation for apoptosis-related proteins, p53, Bcl-2, Bax, caspase-1 and caspase-3 was also performed. The AI was 0.8+/-0.9% (mean+/-SD) before irradiation and 1.7+/-1.3% at the end of the first week of irradiation. We observed that the patients who survived more than 5 years had AI levels of 2.1+/-1.3% at the end of their first week of therapy. This rate was significantly higher than the rate of 1.1+/-0.8% (P=0.02) of the patients who died within 5 years. When the cut-off value of the AI was set at 1.7%, the sensitivity, specificity, positive predictive value, and negative predictive value for the prediction of patients' prognosis after irradiation therapy were 73.4%, 72.4%, 82.4%, and 61.5%, respectively. In 17 of the AI-positive cases, expressions of Bax (P=0.006), caspase-1 (P=0.045), and caspase-3 (P=0.013) at the end of the first week were significantly higher than before irradiation. The proportion of apoptotic cells and the expression of apoptosis-associated proteins, Bax, caspase-1, and caspase-3, at the end of the first week of irradiation could be useful predictors of the prognosis in stage IIIb squamous cell carcinoma of the uterine cervix treated by irradiation therapy.
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PMID:Detection of apoptosis and expression of apoptosis-associated proteins as early predictors of prognosis after irradiation therapy in stage IIIb uterine cervical cancer. 1074 54

We simultaneously assessed bcl-2, bax, bcl-x(L) and bcl-x(S) expression levels by Western blotting on 53 primary untreated cervical cancers and 15 normal samples. Bcl-2 showed a trend to be lower in neoplastic than in normal samples (P<0.01), while no significant difference was observed for bax and bcl-x(L). Bcl-x(S) was barely detectable in only a few samples. Interestingly, in cervical cancer, bcl-2 and bcl-x(L) were directly correlated (P<0. 01). A significant association of bcl-2 levels with age (P<0.021) and menopausal status (P<0.041) in cervical cancer patients as well as in control patients was observed. Bcl-2, bax and bcl-x(L) levels in responding and non-responding patients were not differently distributed. Bcl-2, bax and bcl-x(L) are likely to play a role in the natural history of cervical tumors, but their clinical significance in predicting response to treatment and clinical outcome needs long-term follow-up studies.
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PMID:Bcl-2, bax, bcl-x(L) and bcl-x(S) expression in neoplastic and normal cervical tissue. 1081 75

2-Methylnaphtho[2,3-b]furan-4,9-dione (FNQ3) has been reported to be more cytotoxic to human malignant tumor cell lines than are the corresponding normal epithelial cells. Therefore, we examined the dose response of FNQ3 against human cervical cancer HeLa cells in culture. When 1.25 mg/ml FNQ3 was applied, apoptosis was induced, as determined by an immunohistochemical staining of fragmented genome DNA and cell profiles. Significant inhibition of Bcl-2 oncogene protein expression by the same concentration of FNQ3 also was demonstrated by an immunohistochemical staining method to visualize the expressed cells and Western blot in polyacrylamide gel electrophoresis. Flow-cytometric spectra showed S-phase arrest in cell cycles and the appearance of sub-G1 phase consistent with apoptosis. On the other hand, concentrations of 5 microg/ml or more of FNQ3 induced necrosis. These results show that FNQ3 may act as an antitumor agent to induce apoptosis by affecting Bcl-2 expression and cell cycles, or necrosis as the result of primary mitochondrial injuries.
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PMID:Induced apoptosis and necrosis by 2-methylfuranonaphthoquinone in human cervical cancer HeLa cells. 1097 89

To analyze relevant factors and their effects on neoplastic progression in cervical carcinoma, a panel of genetic markers was studied. Paraffin-embedded tissue sections were obtained from 37 patients with carcinoma of the uterine cervix, 14 noninvasive squamous cell carcinomas (NISCCs), and 23 invasive squamous cell carcinomas (ISCCs). Immunoreactivity of Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax proteins was examined by immunohistochemical staining with appropriate antibodies. Positive staining of Msh2 was detected in 13 of 14 (92.9%) NISCCs and in 13 of 23 (56.5%) ISCCs (P < 0.02). Mlh1 immunoreactivity was observed in 10 of 14 (71.4%) NISCCs and in 8 of 23 (34.8%) ISCCs (P < 0.04). Overexpression of p53 protein was found in 4 of 14 (28.6%) NISCCs and in 16 of 23 (69.6%) ISCCs (P < 0.02). Bcl-2 overexpression was detected in 2 of 14 (14.3%) NISCCs and in 15 of 23 (65.2%) ISCCs (P < 0.003). No significant difference in the two types of lesion was found for Bax and Fhit expression. The relationship between Mlh1, Msh2, and p53 protein expression was significant (P < 0.001 and P < 0.001, respectively), as was that between Fhit and Bax immunoreactivity (P < 0.02). In conclusion, we consider that altered expression of Msh2, Mlh1, p53, and Bcl-2 may be a critical event during cervical cancer progression, whereas Fhit may be a component of a proapoptotic pathway.
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PMID:Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax expression in invasive and in situ squamous cell carcinoma of the uterine cervix. 1099 51

Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death in a variety of tumors. The bcl-2 proto-oncogene is involved in the development of human follicular lymphomas and also in a number of solid tumors such as carcinomas of prostate, breast, lung and GIT. The present study was designed to analyze the role of Bcl-2 expression in cervical intraepithelial squamous neoplasias (CIN) and cervical invasive carcinomas. Special attention was given to the association of Bcl-2 expression with the grade of the lesion, proliferative activity (expression of nuclear antigen of proliferative cells - PCNA) and human papillomavirus (HPV) DNA positivity. We examined tissue samples obtained from 86 women with varying degrees of cervical disease. Bcl-2 and PCNA were investigated using immunohistochemical staining and detection of HPV DNA was performed by hybridization in situ. Increased Bcl-2 expression was observed in advanced degrees of dysplasia and in carcinomas. We found a strong association between the presence of Bcl-2 in pathological epithelium with both the degree of dysplasia and the proliferative activity. We also observed a significant correlation between the amount of Bcl-2 positive lymphocytes infiltrating the lesions and the degree of disease. We, therefore, suggest that Bcl-2 expression in these lymphocytes may influence the antiviral or antitumor immune response. On the other hand we did not detect any significant correlation between the Bcl-2 oncoprotein and the presence of HPV. These results indicate that Bcl-2 may play an important role in the development of cervical cancer.
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PMID:Expression of Bcl-2 in dysplastic and neoplastic cervical lesions in relation to cell proliferation and HPV infection. 1104 35

We have already reported satisfactory therapeutic results of cisplatin-based cyclic balloon-occluded arterial infusion chemotherapy (BOAI) because it enabled advanced cervical cancer of the uterus (cervical cancer) to be treated by simple total hysterectomy (STH). In the present study, we investigated the expression of apoptosis regulatory proteins in advanced cervical cancer treated by cyclic BOAI. The results showed that the proportion of Bax-positive cells was 75.2 +/- 5.6% after the first BOAI in the cases in which STH became possible (group C), and significantly lower, 11.6 +/- 11.7% (p=0.0001), in the cases in which STH remained impossible (group I). The proportion of Bax-positive cells was significantly higher in group C than in group I throughout the treatment period, but there was no significant difference in Bcl-2 expression between the two groups. The survival rate by the Kaplan-Meier method was significantly higher in group C than in group I. These results suggest that the antitumor effect of cyclic BOAI is closely associated with apoptotic cell death, which may in part be influenced by the expression of Bax.
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PMID:Expression of apoptosis regulatory proteins in advanced cancer of the uterine cervix after cyclic balloon-occluded arterial infusion chemotherapy. 1135 Dec 44


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