Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent work suggests that apoptosis is disrupted during the progression of many solid tumors. Isogenic metastatic colon adenocarcinoma cells displayed significantly higher levels of staurosporine-induced apoptosis compared to their nonmetastatic counterparts in vitro. In addition, analysis of 15 matched primary tumors and liver metastases demonstrated that the levels of apoptosis were significantly higher in the metastases, and this increased cell death was associated with significantly lower levels of Bcl-2 protein expression. Our data demonstrate that the molecular events associated with acquisition of the metastatic phenotype sensitize colon cancer cells to some pro-apoptotic stimuli.
 ...
PMID:Increased apoptosis in metastatic human colonic adenocarcinomas. 1219 85

Kupffer cells play an important role in keeping liver from occurrence of tumors. Apoptosis is thought to be a major mechanism responsible for the anti-tumor function of Kupffer cells. Previous studies have mainly concentrated on the direct contact and interaction between Kupffer cells and tumor cells. The present experiment is to investigate the apoptotic pathway in tumor induced by culture supernatant from activated Kupffer cells. The levels of Bax, Bcl-2 and iNOS were analyzed in an in vivo mouse tumor model, which was treated with culture supernatant from activated Kupffer cells. The results showed that the expression of Bax significantly increased while the expression of Bcl-2 decreased when tumor cells were treated with culture supernatants from activated Kupffer cells. The alteration of Bax and Bcl-2 levels resulted in an increase in the ratio of Bax to Bcl-2, which had negative correlation with the size of tumor and positive correlation with the expression of iNOS. The expression of TNF alpha and the occurrence of apoptosis were also increased in tumor treated with culture supernatants from activated Kupffer cells, compared with those which received no treatment. In conclusion, culture supernatants from activated Kupffer cells were able to change the balance between Bax and Bcl-2 in favor of the former. The ratio of Bax to Bcl-2 is a useful index to evaluate tumor apoptosis induced by Kupffer cells. Our experiment also suggests that alteration of the ratio of Bax to Bcl-2 may result from increased levels of iNOS and TNF alpha.
Clin Exp Metastasis 2002
PMID:Negative correlation between the ratio of Bax to Bcl-2 and the size of tumor treated by culture supernatants from Kupffer cells. 1219 74

Reduction in apoptosis has been associated with tumor metastases and response to chemotherapy in breast cancer. We examine the influence of apoptosis status and the expression of antiapoptotic proteins Bcl-2 and Bcl-x(L) on metastatic progression and response to therapy in an experimental model of breast cancer. We used human breast cancer cells (MDA-MB 435, MDA-MB 468 and MCF-7) to induce orthotopic xenograft tumors in nude mice. The overexpression of Bcl-2 or Bcl-x(L) influenced tumorigenicity, 468 transfectants being less tumorigenic than control (p < 0.0001). Lung metastasis appeared at day 120 in animals injected with 435/Bcl-2 or 435/Bcl-x(L) and they showed higher metastatic activity than control 435/Neo tumors (p = 0.02). In contrast, mice with 468 tumors were followed for 1 year after tumor excision, but they did not develop metastatic foci. 435/Bcl-2 and 435/Bcl-x(L) transfectant cells bound less readily to laminin (ANOVA, p < 0.0001), fibronectin (ANOVA, p < 0.0001) and collagen type-IV (ANOVA, p < 0.0001) than 435/Neo cells. The overexpression of antiapoptotic proteins in 435 transfectants rescued 20-40% of cells from anoikis at 64 hr in rocking conditions. In contrast, at this time only 5-10% of 468 and MCF-7 transfectant cells were rescued. Thus, the overexpression of the Bcl-2 or Bcl-x(L) associated with the loss of apoptosis in breast cancer cells in vivo may account for their metastatic behavior. These genes increase tumor metastasis when the oncogenic background has triggered the metastatic process, in which anoikis might determine tumor progression when the life span of the cells is extended.
 ...
PMID:Inhibition of apoptosis in human breast cancer cells: role in tumor progression to the metastatic state. 1220 55

The aim of our study was to elucidate whether and in a what way applying two slightly different immunohistochemical procedures effects Bcl-2 protein detection as well as its relationship to colorectal cancer clinicopathological features. A series of 74 primary colorectal cancers was investigated for expression of the Bcl-2 protein. Two immunohistochemical procedures: first with antigen retrieval using a microwave (art-), second with antigen retrieval by use pressure pot (art+) pre-treatment, were applied in each cancer case. Formalin-fixed, paraffin embedded tissues were treated with ant-Bcl-2 antibody (Dako No M 0887). Bcl-2 (art+) immunostaining was positive in 48 (64.9%) cases of colorectal cancers whereas Bcl-2 (art-) immunohistochemical reaction was positive only in 15 (20%) colorectal tumours. A significant, positive correlation was observed between Bcl-2 (art+) expression and localization of the tumour in the rectum (p = 0.007). At the same time a statistically significant positive correlation between tumour Bcl-2 (art-) expression and colon tumour pT stage (p = 0.007), rectum tumour differentiation grade (p = 0.04) and Bcl-2 (art-) protein immunostaining in lymph node metastases (p < 0.000001) was observed. This data suggest that the type of procedure for antigen retrieval to detection of Bcl-2 protein by immunohistochemical reaction, changes the study results and should be considered when comparing own results with the literature data.
 ...
PMID:Correlation between colorectal cancer Bcl-2 expression and tumour clinicopathological variables. 1253 67

Prostate cancer (Pca) is the most prevalent cancer diagnosed and the second leading cause of cancer-related deaths among men in the Poland. The present study was designed to analyse the relationship between expression of Bcl-2 protein in prostate cancer (PCa) following radical prostatectomy to chosen anatomoclinical and morfological parameters of the tumours. Tumours from 28 patients were assessed by immunohistochemistry. Tissue sections were fixed in 10% buffered formaldehyde solution, embedded in paraffin and stained immunohistochemically with the anti-human Bcl-2 antibody (Dako/Clon124). The immunolocalization of Bcl-2 was performed using the Labelled Streptavidin Biotin (LSAB) method. No correlation was found between Bcl-2 protein expression and pT stage, lymph node metastases, Gleason score, seminal vesicles invasion, positive or negative resection margins as well as capsular penetration and preoperative PSA serum level.
 ...
PMID:Bcl-2 immunohistochemical detection in prostate cancer. 1253 68

We investigated the effects of interleukin-2 (IL-2) exposure on T-cell signal transduction molecules and apoptosis markers in tumour-infiltrating lymphocytes (TIL) isolated from 20 melanoma and 16 colorectal carcinoma metastases and expanded in vitro for therapeutic reinfusion. Before IL-2 culture, TIL showed undetectable or very low levels of T-cell receptor (TCR) epsilon chain, p56(lck), Fas ligand (FasL) and Bax expression, while Bcl-2 values were elevated. Cancer cells were characterised by low or absent Fas and Bcl-2 and high Bax expression. Notably, they also expressed FasL. After 41-48 days of IL-2 culture, TCR epsilon chain and p56(lck) expression of TIL rose to median values of approximately 80 and 30% positive cells, respectively (P<0.001), FasL expression was detected in 45% cells from melanomas (P<0.001) and in 3% from colorectal carcinomas (P=0.09), and Bax-positive cells increased from 17.5 to 70% (P=0.005). Moreover, TCR zeta chain-positive cells were significantly increased from baseline (P=0.001), Bcl-2-positive cells dropped from 50 to 1% (P=0.007) and perforin content was high, while Fas expression was not significantly modified by IL-2 culture. In conclusion, our data suggest that the degree of immunosuppression in TIL from melanomas and colorectal carcinomas is very high, and the apoptosis markers' repertoire of cancer cells resembles that of immune-privileged tissue. Interleukin-2 culture appears to restore lymphocyte activation mechanisms, resulting in consistent FasL expression and perforin production.
 ...
PMID:Restored T-cell activation mechanisms in human tumour-infiltrating lymphocytes from melanomas and colorectal carcinomas after exposure to interleukin-2. 1261 May 20

The formation of poorly-differentiated clusters of cancer cells in the tumour growth zone, defined as "tumour budding", is a likely factor determining the biological malignancy of colorectal cancer (CRC). The aim of the study was to evaluate tumour budding in the CRC growth zone and to analyse its relationship to chosen anatomoclinical parameters, and to p53 and Bcl-2 protein expression in the tumour budding and in the main tumour mass. Fifty-seven colorectal cancers, classified as pT3 and G2, were used for analysis. Immunohistochemical investigations were performed using the anti-human p53 and Bcl-2 protein monoclonal antibodies (Dako/p53, No M7001 and Dako/Bcl-2, No M 0887, respectively). It has been found that p53 overexpression in the primary tumour and the presence of lymph node metastases correlate with strongly-positive tumour budding (p < 0.04 and p < 0.000001). However, low expression of p53 protein in the primary tumour and lack of lymph node metastases was statistically significantly correlated with the absence of tumour budding. A statistically significant correlation was shown between p53 protein expression in the tumour budding and expression of p53 in the primary tumour and lymph node metastases (p < 0.05). We also observed a statistically significant correlation between Bcl-2 protein expression in the tumour budding and its expression in the primary tumour and lymph node metastases (p < 0.05). These data suggest that tumour budding of cancer, in combination with other markers, may provide more information about the biological behaviour of colorectal cancer.
 ...
PMID:Tumour 'budding' and its relationship to p53 and Bcl-2 expression in colorectal cancer. 1268 Jan 62

This study was designed to examine the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and bcl-2 protein in 45 cases with advanced laryngeal squamous cell carcinoma who had undergone total laryngectomy with unilateral modified radical neck dissection, and the relation of this expression to some prognostic factors such as tumor front grading and neck lymph node metastases. Sections were reevaluated for routine histologic grade, tumor front grading and neck lymph node metastases, and were stained with monoclonal antibodies against PCNA and bcl-2. Significant correlation was present between the severity of PCNA expression and incidence of lymph node metastasis (p<0.05). No correlation was found between the severity of PCNA expression and tumor front grading. Bcl-2 expression did not associate with either parameters. In conclusion, PCNA is important in predicting prognosis and no association is present between the bcl-2 protein expression and prognostic factors.
 ...
PMID:Correlation of proliferating cell nuclear antigen and bcl-2 expression with tumor front grading and metastasis in laryngeal squamous cell carcinoma. 1274 Jun 49

Melanoma begins with benign nevi and progresses to radial growth phase (RGP) and to vertical growth phase [(VGP), metastatic phenotype]. The molecular changes associated with these transitions are not yet well defined. However, transcriptional regulation of some genes that are critical in melanoma progression is beginning to be elucidated. The first part of this review will focus on our recent studies demonstrating that progression of human melanoma is associated with loss of expression of the transcription factor AP-2. In metastatic melanoma cells, this loss resulted in overexpression of MCAM/MUC18 and MMP-2, and lack of expression of c-KIT. In further investigations, we inactivated AP-2 in SB-2 primary cutaneous melanoma cells by using a dominant-negative AP-2, the AP-2B gene. Expression of AP-2B in SB-2 cells augmented their tumorigenicity in nude mice and upregulated MMP-2 expression and activity. We have also recently demonstrated that loss of AP-2 expression in metastatic melanoma cells resulted in overproduction of the thrombin receptor, PAR-1. Other studies have shown that AP-2 regulates additional genes involved in melanoma development and progression, including E-cadherin, p21/WAF-1, HER2, Bcl-2, FAS/APO-1, IGF-R-1, and VEGF. We propose that loss of AP-2 is crucial in the development of malignant melanoma. Additionally, the transition of melanoma cells from RGP to VGP is associated with overexpression of two transcription factors, CREB and ATF-1, both of which may act as survival factors for human melanoma cells. The second part of the review will briefly discuss the role of other transcription factors, including ATF-2, SNAIL, MITF, and NFkappaB in the progression of human melanoma and will summarize recent knowledge on how changes in the expression of these transcription factors contribute to acquisition of the metastatic phenotype in human melanoma.
Clin Exp Metastasis 2003
PMID:Transcriptional regulation of metastasis-related genes in human melanoma. 1274 83

To form metastases, tumors must break from the primary tumor site, invade surrounding tissues, enter and survive within the circulation and ultimately colonize a distal tissue. Each of these steps requires the cooperative function of numerous proteins--proteins that facilitate angiogenesis (e.g., VEGF), cell survival (e.g., Bcl-2), invasion (e.g., MMPs), and autocrine growth stimulation (e.g., c-myc, cyclin D1). Although expression of these proteins is regulated at many levels by disparate stimuli, translation of these key malignancy-related proteins is regulated primarily by the activity of the mRNA cap-binding protein eIF-4E, the rate-limiting member of the eIF-4F translation initiation complex. By binding the cap structure at the 5' terminus of cellular mRNAs, eIF-4E recruits mRNAs to the eIF-4F complex, which then scans from the 5' cap through the untranslated region (5'UTR), unwinding secondary structure to reveal the translation initiation codon and to enable ribosome loading. Messenger RNAs with short unstructured 5' UTRs are more easily translated than mRNAs harboring lengthy, highly structured 5' UTRs, as these prohibit efficient scanning and start codon recognition. As such, the translation of these mRNAs, which typically encode proteins involved in angiogenesis (e.g., VEGF), tumor growth (cyclin D1) and survival (Bcl-2), is suppressed except when eIF-4E is engaged with the eIF-4F complex--a common event in many human and experimental cancers. This review focuses on the hypothesis that enhanced eIF-4E function contributes to metastatic progression by selectively upregulating the translation of key malignancy-related proteins that together conspire to drive the metastatic process.
Clin Exp Metastasis 2003
PMID:Translational control and metastatic progression: enhanced activity of the mRNA cap-binding protein eIF-4E selectively enhances translation of metastasis-related mRNAs. 1274 84


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>