Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Betel quid (BQ) chewing has been a well-documented cause of oral epithelial lesions (OEL). Evolution from early hyperplastic lesions to the late or carcinomatous stage has been recognized. The pathobiological and molecular mechanism, however, remains to be elucidated. In this study, a total of 232 samples obtained from 153 cases of BQ-related OEL were retrospectively evaluated for the expression of p53 and bcl-2 in comparison with 26 cases of BQ-unrelated lesions (n = 29). The possible role of human papillomavirus (HPV) was also investigated. These BQ-related OELs included verrucous hyperplasia (VIH, n = 57, 24.6%), epithelial dysplasia (n = 23, 9.9%), verrucous carcinoma (VC, n = 5, 2.1%) and squamous cell carcinoma (SCC, n = 106, 45.7%). Fifty-four cases (35.3%) had multiple lesions. In comparison with the BQ-unrelated OELs, the characteristics of BQ-related OELs were a younger age, male predilection and multicentricity. In contrast to the tongue in BQ-unrelated OELs, the most common site for all types of BQ-related lesions was the buccal mucosa. Immunohistochemical studies of BQ-related lesions showed p53 staining in 30% of dysplasia and 38% of SCC, but a consistent absence in VH and VC. The cases with p53-positive SCC had a higher recurrence rate than p53-negative ones. Bcl-2 expression was negligible for all types of lesions. HPV-6/11 was detectable in 10% of dysplasia and 13% of SCC, but in neither VH nor VC. HPV-16/18, however, was consistently negative for all types of lesions. Our data suggest that p53, but not bcl-2, may play a role in tumor progression of BQ-related OELs, and that VH and VC are distinct and closely related histological lesions. The consistent absence of the malignant-type HPV in all BQ-related lesions suggests that HPV plays an insignificant role in the tumorigenesis of BQ-related oral cancers, although a cooperative role may exist between the benign-type HPV and BQ chewing.
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PMID:Pathological features of betel quid-related oral epithelial lesions in taiwan with special emphasis on the tumor progression and human papillomavirus association. 1241 91

Apoptosis is induced by many kinds of therapy-related inducers, such as hyperthermia and chemotherapeutic agents. However, differences in apoptotic pathways between these inducers remain unclear, although knowing the differences is important to map out a therapeutic strategy. Therefore, we focused on the localization and phosphorylation of Bcl-2 and Bax, key mediators of the apoptotic pathway, after hyperthermia and paclitaxel treatment of PC-10 squamous cell carcinoma cells that excessively expressed Bcl-2 and Bax in the cytoplasm. Paclitaxel treatment markedly induced qualitative changes in Bcl-2, whereas hyperthermia did only quantitative changes in Bax. The levels of Bax increased gradually with the duration of hyperthermia, whereas Bcl-2 levels slightly decreased. On the other hand, paclitaxel treatment induced dose- and time-dependent phosphorylation of Bcl-2. Interestingly, phosphorylated Bcl-2 was observed in the specific subcellular sites, mitochondria- and lysosome-rich fractions. Both treatments disturbed the heterodimerization of Bax with Bcl-2. Hyperthermia, but not paclitaxel treatment, induced a gradual Bax translocation from the cytoplasm to the nucleus. Although both treatments induced a prominent cell cycle disturbance in the G2M phase, paclitaxel treatment induced typical apoptosis, and hyperthermia hardly induced apoptosis. Our results suggest that the subcellular redistribution of Bax and the phosphorylation of Bcl-2 depend on the type of apoptosis inducers, such as hyperthermia and paclitaxel, and Bcl-2 has a central role in the decision of apoptotic outcome. Our data may afford new insights in apoptosis from the aspect of an association of Bcl-2 phosphorylation with intracellular Bax localization.
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PMID:An association of Bcl-2 phosphorylation and Bax localization with their functions after hyperthermia and paclitaxel treatment. 1245 53

Flavopiridol is a synthetic flavone that inhibits tumor growth by suppressing cyclin-dependent kinases (CDKs). We have investigated effects of flavopiridol in oral squamous cell carcinoma (OSCC). Flavopiridol was found to inhibit the growth of OSCC cells in a time- and dose-dependent manner. Induction of apoptosis was observed in all cells showing accumulated cells with sub-G(1) DNA contents, DNA fragmentations, and PARP cleavages. While Bcl-2 and Bax expression did not change, Bcl-x(L) was down regulated and Bcl-xs was up-regulated after being exposed to flavopiridol. Flavopiridol treatments also resulted in remarkable reductions of cyclin A, cyclin B, and cyclin D1 expressions. We also found that expression levels of CDK activation kinase and CDC25C were reduced, and p34 inactive form CDK2 were up-regulated. Our data indicate that flavopiridol has growth inhibition activities against OSCC. Flavopiridol not only inhibits CDKs directly, but it also inhibits the CDKs activation pathway and activates the Bcl-x apoptotic pathway.
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PMID:Flavopiridol, a cyclin dependent kinase (CDK) inhibitor, induces apoptosis by regulating Bcl-x in oral cancer cells. 1245 21

Deregulation of cell-cycle G(1)-restriction point control by disruption of Rb-pathway components is a frequent event in cancer. In concert with the inactivation of cell death pathways, such events not only contribute to tumor development but also determine the intrinsic and acquired resistance to cancer therapy and, ultimately, disease prognosis. We previously observed that the cyclin-dependent kinase inhibitor p16(INK4a) and the proapoptotic Bcl-2 homolog Bax are positive prognostic factors and identify patients with good prognosis in esophageal squamous cell carcinoma (SCC). In the present study, we therefore extend our analysis to additional genes controlling the G(1) restriction point and apoptosis, respectively. This retrospective analysis was performed in a cohort of 53 patients undergoing surgery for esophageal SCC with curative intent, i.e., R0 resection. Protein expression profiles of cyclin D1, p16(INK4a), Rb, p21(CIP/WAF-1), p53, Bax and Bcl-2 were analyzed by immunohistochemistry and compared to p53 mutational status, as determined by SSCP-PCR of exons 5-8. Loss of p16(INK4a), Rb, p21(CIP/WAF-1) or Bax and overexpression of cyclin D1 were associated individually with shorter overall survival, while Bcl-2 expression and p53 mutation were not of prognostic relevance. The longest survival was observed in a subgroup of patients whose tumors bore a combination of favorite genotypes, i.e., low cyclin D1 and high Rb, p21(CIP/WAF-1), p16(INK4a) and Bax protein expression. These results show that multigene analyses based on limited sets of functionally linked genes reliably identify patients with good vs. poor prognosis.
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PMID:Multigene analysis of Rb pathway and apoptosis control in esophageal squamous cell carcinoma identifies patients with good prognosis. 1247 59

Carboplatin (CBDCA) has been widely used for the treatment of oral squamous cell carcinoma (SCC). The Bcl-2 family member Bcl-xL has been demonstrated to provide resistance to chemotherapeutic agents including CBDCA. Morpholino Bcl-xL antisense oligonucleotides (oligos) were employed to down-regulate Bcl-xL in CBDCA-resistant (MIT8, MIT16) as well as CBDCA-sensitive (MIT7) SCC cell lines. The oligos were delivered to adherent cells using a scrape-load procedure. The Bcl-xL antisense reduced Bcl-xL levels without altering the level of control actin, suggesting the specificity of this agent. The addition of Bcl-xL antisense oligos substantially prevented the cell growth of both CBDCA-sensitive and-resistant cells. The CBDCA-induced partial prevention of cell growth was further augmented by the addition of the Bcl-xL, but not the control, antisense oligos. The morpholino type Bcl-xL antisense oligos may be useful for the treatment of SCC, especially multidrug-resistant tumors with enhanced Bcl-xL levels.
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PMID:BcI-xL antisense treatment sensitizes Bcl-xL-overexpressing squamous cell carcinoma cells to carboplatin. 1257 53

The chronological changes in intracellular Ca(2+)concentrations ([Ca(2+)](i)) were analysed during heat-induced apoptosis in human lung cancer cell lines LK-2 (squamous cell carcinoma) and LU65A (large cell carcinoma). In LK-2 cells, increased [Ca(2+)](i) levels were maintained at levels between 250-350 nm 9 h after heat-shock. Treatment with BAPTA, an intracellular Ca(2+) chelator, prior to heat-shock, decreased the frequency of heat-induced apoptosis in LK-2, while thapsigargin, a selective endoplasmic reticulum Ca(2+)-ATPase inhibitor, did not change the number of apoptotic cells, regardless of the presence or absence of Ca(2+)-supplemented medium. In LU65A cells, treatment with BAPTA or thapsigargin did not alter the apoptotic rates. Western blotting demonstrated that, although expression of Bax and Bcl-2 were not changed by heat-shock, p53 expression was elevated in LK-2, but not LU65A cells. Immunohistochemistry showed that p53 was localized predominantly in the cytoplasms of LK-2 cells, suggesting that p53 protein is not functional in LK-2. Heat-shock also elevated activities of caspase-3, -8 and -9 in both cell lines. It is concluded that a temporal increase in [Ca(2+)](i) is the important initiating factor in hyperthermia-induced apoptosis in LK-2 cells and that, in these two lung cancer cell lines, apoptosis may occur through 'cross-talk' between p53-independent mitochondrial and death receptor pathways.
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PMID:Elevated levels of intracellular Ca2+ and apoptosis in human lung cancer cells given heat-shock. 1262 40

Squamous cell carcinoma is the most common malignant neoplasm of the oral cavity. Number of mechanisms plays a role at the molecular level to transform normal cell into a neoplastic cell. There are a gamut of genes, which are expressed among which bcl-2, have gained a unique importance as inhibitor of apoptosis. In normal epithelial cells Bcl-2 is restricted to stem cells and cells which undergo mitosis. Bcl-2 blocks the post-mitotic phase from apoptosis. Reports of Bcl-2 protein expression in carcinomas are conflicting such as down regulation to elevated expression. In the present study 67 cases of squamous cell carcinomas of varying grades were studied and uniform cytoplasmic positivity were noted in 12 cases for Bcl-2 protein. Bcl-2 prolongs cell survival in epithelial cells and there by giving way to other external stimulus like action of carcinogens and viral agents and interaction with other genes and aids in progression to neoplasia. The possible roles of bcl-2 in the pathogenesis of oral squamous cell carcinoma are discussed.
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PMID:Expression of bcl-2 oncoprotien in oral squamous cell carcinoma--an immunohistochemical study. 1278 67

Bcl-2 inhibits most kinds of programmed cell death and provides a selective survival advantage to various cell types. The biological significance of Bcl-2 expression for the development and progression of oral cancer has still to be evaluated. The aim of our study was to estimate possible correlations between the Bcl-2 protein expression and some clinicopathological features of oral cancer. The study was conduced on 129 patients treated surgically for oral squamous cell carcinoma. The statistically significant relationships were observed between oral squamous cell cancer Bcl-2 expression and higher tumor grading (p<0.005), higher tumor mitotic index (p<0.005), higher index of atypical mitoses (p<0.001) as well as microfocal pattern of tumor invasive margin (p<0.001). The results suggest that positive Bcl-2 expression may be a valuable factor supplementing the established unfavorable histopathological features of oral squamous cell carcinoma.
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PMID:Correlation between Bcl-2 protein expression and some clinicopathological features of oral squamous cell carcinoma. 1281 80

It has been previously demonstrated that human carcinomas express interleukin-2 receptor (IL-2R) alpha, beta, and gamma chains. The beta and gamma chains of IL-2R have intermediate binding affinity for IL-2 and are responsible for the intracellular signaling cascades after IL-2 stimulation. IL-2Ralpha lacks the cytoplasmic domain, but is essential for increasing the IL-2-binding affinity of other receptors. Overexpression of IL-2Ralpha in tumor cells is associated with tumor progression and a poor patient prognosis. To define molecular mechanisms responsible for the effects associated with IL-2Ralpha expression, ex vivo experiments were performed with the squamous cell carcinoma head-and-neck cancer line, PCI-13, which was genetically engineered to overexpress the IL-2Ralpha chain. While IL-2Ralpha-overexpressing PCI-13 cells were capable of forming colonies in soft agar, PCI-13 cells transfected with the control vector or those expressing IL-2Rgamma did not. Consistently, IL-2Ralpha-expressing tumor cells proliferated more rapidly than the control or IL-2Rgamma+ cells, associated with increased levels of cyclins A and D1 and cyclin-dependent kinase (cdk(s)) 2 and 4 proteins. In addition, IL-2Ralpha-expressing cells were significantly more resistant to apoptosis induction by a tripeptidyl proteasome inhibitor (ALLN) and two chemotherapeutic drugs (VP-16 and taxol) than the control or IL-2Rgamma+ cells. Accompanying the drug resistance, high levels of anti-apoptotic Bcl-X(L) and Bcl-2 proteins were found in the mitochondria-containing fraction of IL-2Ralpha-expressing tumor cells. Treatment of IL-2Ralpha-expressing cells with a specific Janus kinase 3 (Jak3) inhibitor decreased expression of cyclin A, cyclin D1, Bcl-X(L), and Bcl-2 proteins. Finally, high levels of ubiquitinated proteins were detected in the proliferating IL-2Ralpha-expressing cells. Our data suggest that increased proliferation rates and decreased drug sensitivity of IL-2Ralpha-expressing tumor cells are responsible for the enhanced tumor aggressiveness and poor clinical prognosis of patients whose tumors express IL-2Ralpha.
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PMID:Overexpression of interleukin-2 receptor alpha in a human squamous cell carcinoma of the head and neck cell line is associated with increased proliferation, drug resistance, and transforming ability. 1285 47

Regulation of apoptosis by extracellular molecules binding to cell death receptors has received much attention in recent years. Fas, a member of the tumor necrosis factor receptor superfamily, is a transmembrane protein whose extracellular domain binds its cognate ligand (FasL), which can induce apoptosis in sensitive cells. Fas ligation leads to activation of cell death proteases, thereby initiating a proteolytic cascade which results in cellular fragmentation and death. Apoptosis is also regulated by inhibitory signals which promote cell survival. The bcl2 family of proteins is composed of both inhibitors and activators of programmed cell death. The bcl2 protein itself inhibits many apoptotic stimuli while other members of the bcl2 family such as bak and bid promote cell death. Many types of cancer chemotherapy induce cellular stress leading to induction of apoptosis. Stress-activated protein kinases such as p38 have been shown to inactivate bcl2 through phosphorylation and induce cleavage of bid. Deficiency of proapoptotic bcl2 family members has been associated with drug-resistant phenotypes. We report that exposure of human squamous cell carcinoma lines to different chemotherapy drugs activates a caspase cascade which is distinct from that of receptor-mediated apoptosis. The variable sensitivity of each cancer cell line to different forms of chemotherapy was not due to differences in caspase or bcl2 family protein expression. Rather, the stress-activated protein kinase p38 was overexpressed by resistant SCC lines which correlated with reductions in proapoptotic bid and bak protein expression. These two proteins exhibit distinct patterns of intracellular localization during chemotherapy-induced apoptosis.
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PMID:A common pathway for chemotherapy-induced apoptosis in human squamous cell carcinoma lines distinct from that of receptor-mediated cell death. 1289 10


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