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)

Epstein-Barr virus (EBV) is associated with tumours of both lymphoid and epithelial origin. Whilst a role for EBV latent genes in the development of these malignancies is accepted, it is also possible that viral proteins involved in EBV replication may influence the oncogenic process. BHRF1 is an immediate early protein which has homology with the Bcl-2 oncogene and can protect B cells from apoptosis. In vivo this protein is most abundantly expressed in the upper layers of oral 'hairy' leukoplakia (HL), a benign hyperparakeratotic tongue lesion which represents a focus EBV replication. We have transfected BHRF1 into the human squamous cell carcinoma line SCC12F which retains several features of normal keratinocytes behaviour in vitro. BHRF1 expression in these epithelial cells is associated with a delay in the commitment of cells to terminal differentiation, increased resistance to the DNA damaging drug, cis-platin and enhanced survival under conditions of serum deprivation. As the differentiation of epithelial cells is an apoptotic process, this data strongly suggests that BHRF1 expression delays the terminal differentiation of epithelial cells through the prevention of apoptosis. This effect of BHRF1, which may normally function to promote productive EBV infection, could contribute to the development of EBV-associated tumours.
 ...
PMID:BHRF1, a viral homologue of the Bcl-2 oncogene, disturbs epithelial cell differentiation. 782 80

Although the pathogenesis of leukoplakia has been unclear, carcinogenic transformation is postulated to result from alterations of apoptotic signal transduction proteins in epithelial cells. The pathogenesis of oral lichen planus (OLP) has also been unclear, but apoptotic changes of the epithelial cells in OLP have been reported. In the present study, we used a histochemical approach to describe human keratinocyte-expression of several apoptotic signaling proteins in leukoplakia, in OLP, and in normal oral mucosa as a control. Mucosal biopsies from patients with leukoplakia (n=13), OLP (n=10), and normal oral mucosa (n=9) were frozen, sectioned and immunostained with monoclonal antibodies to wild-type (wt) tumor suppressive protein p53, cyclin-dependent kinase inhibitor p21WAF1/CIP1 and the oncoproteins MDM2, and Bcl-2. Apoptosis was assessed in all cases by the TUNEL method. MDM2 and Bcl-2 expression in keratinocytes were quantitatively greater in leukoplakia than in OLP. Wt-p53 and p21WAF1/CIP1 expression was quantitatively greater in keratinocytes in OLP than in leukoplakia. Keratinocyte maturation appeared histologically normal in OLP, even though wt-p53 and p21WAF1/CIP1 were expressed in these cells. Altered keratinocyte maturation was seen in leukoplakia lesions expressing MDM2 and Bcl-2. No significant difference for the number of apoptotic epithelial cells was observed between leukoplakia and OLP, in spite of the divergent outcomes of the apoptotic signaling proteins.
 ...
PMID:Expression of apoptotic signaling proteins in leukoplakia and oral lichen planus: quantitative and topographical studies. 1097 47

The oral cavity is continually exposed to various traumas due to the effect of thermal, mechanical and chemical stimuli, which when accompanied by inflammatory states may promote the growth of neoplastic changes. Numerous studies have revealed a correlation between the expression of p53 and Bcl-2 proteins and the progression of neoplastic disease. It cannot be excluded that these proteins act as biomarkers of a neoplastic transformation threatening in precancerous states (including leukoplakia) or the already existing neoplastic transformation (e.g. in oral squamous cell carcinoma). The aim of the study was to evaluate the expression of p53 and Bcl-2 proteins in the proliferating epithelium in relation to leukoplakia degree and with regard to the lesions accompanied and not accompanied by squamous cell carcinomas. Fifty-five cases of proliferating changes in the oral epithelium (leukoplakia) were investigated. Group I contained 20 leukoplakias not accompanied by oral squamous cell carcinomas. Groups II, III and IV included 35 cases of changes in the vicinity of carcinomas on the lower lip (group II), in the front 2/3 of the tongue (group III) and in the oral floor (group IV). Staining was performed according to the immunohistochemical method with the use of monoclonal antibodies against human p53 protein (DAKO No M7001) and Bcl-2 (DAKO No M0887). A higher expression of p53 protein (54%) was found in leukoplakia changes coexisting with squamous cell carcinomas, compared with the non-accompanied ones (p53--45%). The results indicate a correlation between epithelial dysplasia degree and p53 and Bcl-2 protein expression--severe dysplasia occurred with an increase in the expression of both proteins. Leukoplakias situated in the vicinity of squamous cell carcinomas showed higher expression of p53 and Bcl-2 compared with the non-accompanied alterations. A correlation was also revealed between the location and p53 and Bcl-2 protein expression degree in the non-accompanied changes; no such correlations were found in proliferating epithelial changes adjacent to neoplastic tumors.
 ...
PMID:Evaluation of p53 and bcl-2 oncoprotein expression in precancerous lesions of the oral cavity. 1147

The aim of this study was immunolabeling oncoproteins Ck14, p53, p21 and Bcl-2 in order to evaluate their expression in premalignant and malignant stomatological lesions in oral epithelial, and to compare this expression with exfoliative cytology alterations in the same patients. It was studied biopsies and cytologies of 13 subjects with oral lichen planus, with or without Human Papilloma Virus (HPV), leukoplakia and squamous cell carcinoma clinically diagnosed and confirmed by anatomopathological studies. The oral lichen planus lesion presented binuclei orange cells; and in leukoplakia lesions only orange stained was observed; meanwhile koilocytes, inflammatory cells, enlarge nuclear volume and pathogenic microorganisms were observed in the HPV infections and squamous cells carcinoma (SCC). The Ck14, p53, p21 and Bcl-2 proteins were found modified in the leukoplakia, oral lichen planus and cancer. Cytological alterations and positive immunolabeling or over-expression of Ck14 cytokeratine in the upper epithelial stratus should be indicator of malignant transformations as doing subsequence exams.
 ...
PMID:Valuation of exfoliative cytology as prediction factor in oral mucosa lesions. 1599 78

Oral cancer accounts for 40 to 50% of cancers diagnosed in India. Oral cancer is preceeded in most cases by pre malignant lesions-leukoplakia, submucous fibrosis and lichen planus. Stoppage of causative agents reverts premalignant lesions in some of the cases only. Thus anti oxidant therapy is being used to revert premalignant change to normal. Few studies available, have taken clinical parameters as indicators of response to therapy. Extensive medline search failed to reveal any study at the cellular level. This study attempts to investigate for the first time the role of p53 and bcl2 as markers of prognosis following vitamin A therapy. 24 cases of pre malignant lesions of oral cavity were studied. 1 lakh IU of vitamin A were given orally twice a week for 3 months. Biopsies were done before and after therapy. Haematoxylin and Eosin stain was done to confirm diagnosis. Immunostaining for mutant p53 and bcl2 was done on paraffin sections. 500 cells were counted over an average of 5 HPF and percentage positivity was calculated. Statistical analysis was done by applying the paired t tests. In 19 cases (79.2%) of premalignant lesions mutant p53 expression was zero before therapy, and remained unchanged even after the therapy. 3 cases (12.5%) had high mutant p53 values which reduced following therapy (p = 0.037). Therapy thus proved effective in these cases. However, in 2 cases (8.3%) pre therapy values of zero showed an increase after vitamin A therapy. These were the cases which had dysplasia and were chronic smokers. In 2 cases (8.3%) pre therapy values of bcl2 were zero and remained unchanged even after therapy and these cases did not stop smoking even during the vitamin A therapy. In 12 cases (50.0%) higher pre therapy values were reduced after therapy (p < 0.0001). Vitamin A therapy was effective in these cases. However, in 10 cases (42.0%) expression of bcl2 increased subsequent to therapy. Therapy failed in these cases because of chronic heavy smoking and tobacco chewing. Thus, in the majority of cases vitamin A was effective in preventing mutation of p53 (91.7%) and expression of bcl2 (58.0%). In effect, these two oncoproteins can be used as prognostic markers and follow up for anti oxidant therapy.
 ...
PMID:Role of p53 and bcl2 as markers of vitamin A response in premalignant lesions of the oral cavity. 1747 47

Expression of Bcl-2 family proteins in tumours can modulate apoptosis, influencing tumour behaviour and treatment. To investigate their role in oral tumourigenesis, nine Bcl-2 family transcripts were examined in three oral cell lines and 25 oral tumours, using ribonuclease protection assay. Since Mcl-1 mRNA was elevated in these samples, Mcl-1 splice variants were assessed by RT-PCR and Mcl-1 protein was studied in normal, premalignant and malignant oral tissues and cell lines, by immunohistochemistry and/or immunoblotting. The cell lines exhibited significantly higher levels of 7/9 Bcl-2 family transcripts as compared to those in normal tongue, and significantly higher (p=0.030, p=0.004) anti-apoptotic versus pro-apoptotic transcripts. Elevated Mcl-1 mRNA was observed in 11/25 (44%) tumours as compared to normal tissues with a five- to ten-fold higher expression of full-length anti-apoptotic Mcl-1 transcript versus the pro-apoptotic short isoform. Strong cytoplasmic Mcl-1 immunoreactivity was detected predominantly in differentiated epithelia in 27/33 (82%) oral tumours, 18/20 (90%) leukoplakia, 25/30 (83%) submucous fibrosis and 3/3 oral cell lines, with weak staining in 8/15 (53%) normal mucosa samples. Mcl-1 positivity in malignant and premalignant tissues was comparable but significantly higher (p<0.01) than that in normal mucosa. The expression of bcl-2 family genes, including Mcl-1 in tumours, did not correlate significantly with clinicopathological parameters. This is the first report delineating the in vivo expression patterns of Mcl-1 protein and Mcl-1 transcripts in oral cancers and premalignant lesions. The observed imbalance between expression of anti-apoptotic and pro-apoptotic Bcl-2 family genes may promote survival in the oral cell lines. Since the majority of oral tumours associated with tobacco-chewing evolve from premalignant lesions, the sustained expression of full-length anti-apoptotic Mcl-1 protein in these tissues suggests an important role for Mcl-1, early in oral cancer pathogenesis in protecting cells from apoptosis via neutralization of pro-apoptotic members and could be a potential therapeutic target for oral cancers.
 ...
PMID:Human oral cancers have altered expression of Bcl-2 family members and increased expression of the anti-apoptotic splice variant of Mcl-1. 1900 87