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)

Insufficient apoptosis is implicated in many human cancers, including cervical carcinoma. The objectives of this study were to explore changes of apoptosis-regulating gene expression and their clinical significance in cervical cancer. The expression of apoptosis-regulating genes, including five Bcl-2 family and two caspase family members, was evaluated in 43 cervical invasive squamous cell carcinomas, using immunohistochemistry. Specimens in which >or=10% of the neoplastic cells showed cytosolic immunoreactivity were considered to be immunopositive. Results were correlated with clinico-pathologic characteristics of the subjects. All seven apoptotic regulators examined were positive in a proportion of the tumors. The percentage of cases expressing Bax was higher in the patients without evidence of disease after treatment than in the patients alive with disease or who died of disease (P<0.05). A significant difference in disease-free survival was detected between Bax-positive and -negative groups (P<0.05), and in overall survival between Mcl-1-positive and -negative groups (P<0.05). Significant association between the seven markers tested was only found for caspase 3 and Bak immunoreactivity in cervical carcinoma (P<0.05). The results demonstrate expression of multiple apoptosis-modulating proteins in cervical cancer. There appears to be complex regulation of apoptosis protein levels in association with clinical behavior of cervical squamous cell carcinoma.
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PMID:Expression of apoptotic regulators and their significance in cervical cancer. 1191 71

DEPTOR is an endogenous inhibitor of mTOR complexes, de-regulated in cancers. The present study reveals a vital role for DEPTOR in survival of cervical squamous cell carcinoma (SCC). DEPTOR was found to be overexpressed in both cervical SCC cells and tissues and it's silencing in cervical SCC cells induced apoptosis, mainly by up-regulation of p38 MAPK and by inhibiting PI3K/AKT pathway via a feed-back inhibition from mTORC1-S6K. DEPTOR silencing resulted in reduced expression of the nitric oxide synthases iNOS and eNOS, as well as increased activation of ERK1/2 and p38 MAP kinases. Activation of AKT signaling by overexpression of constitutively active-AKT (CA-AKT) failed to overcome the apoptosis caused by DEPTOR silencing. Similarly pharmacological inhibition of ERK also failed to control apoptosis. However pharmacological inhibition of p38 MAPK rescued the cells from apoptosis, indicating the major role of p38 MAPK in cell death induced by DEPTOR silencing. DEPTOR was also found to regulate ERK1/2 in an AKT dependent manner. DEPTOR knockdown induced cell death in SiHa cells overexpressing the anti-apoptotic Bcl-2 and Bcl-xL, indicating strong survival role of DEPTOR in these cells. DEPTOR overexpression activated PI3K/AKT by relieving the negative feed-back inhibition from mTORC1-S6K. DEPTOR regulation was also observed to be independent of HPV E6/E7 oncoproteins, but it might be a molecular co-factor contributing to cervical carcinogenesis. In summary, DEPTOR is found to promote survival of cervical SCC cells and its reduction induced apoptosis via differential effects on PI3K/AKT and p38 MAPK and can be a potential target in cervical SCC.
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PMID:DEPTOR promotes survival of cervical squamous cell carcinoma cells and its silencing induces apoptosis through downregulating PI3K/AKT and by up-regulating p38 MAP kinase. 2699 19

To explore the possible influence of deleted in malignant brain tumor 1 (DMBT1) in cervical squamous cell carcinoma (CSCC). DMBT1 expression was detected by Real-time reverse transcription PCR (qRT-PCR) and immunohistochemistry in CSCC and adjacent normal tissues from 167 CSCC patients, and its relationship with clinicopathological features and prognosis was analyzed. Besides, the in vitro experiments, including MTT, Cell-Light EdU, Wound-healing, Transwell invasion, Annexin V-FITC/PI staining, qRT-PCR, and Western blot, were performed in SiHa and CaSKi cells, which were both divided into Blank, Vector, and DMBT1 groups. The mRNA level and the positive expression rate of DMBT1 in CSCC tissues were lower than the adjacent normal tissues. Moreover, DMBT1 positive rate was linked to FIGO stage, tumor diameter, lymph node metastasis, and tumor differentiation of CSCC. Besides, patients with positive DMBT1 expression had higher 5-year survival rate than those negative ones. According to the in vitro experiments, SiHa and CaSKi cells with overexpressed DMBT1 showed the inhibition of proliferative ability and the enhancement of apoptosis with the upregulated pro-apoptosis proteins (Bax and Cleaved caspase-3) and down-regulated anti-apoptosis protein Bcl-2. Moreover, compared with Blank group, DMBT1 group presented decrease in the migration and invasion of SiHa and CaSKi cells with the down-expression of interstitial markers (N-cadherin and Vimentin) and the up-expression of epithelial marker E-cadherin. DMBT1 was decreased in CSCC, whereas its overexpression can not only inhibit the proliferation, migration, and invasion, but induce the apoptosis of human CSCC cells, being a novel strategy for CSCC treatment.
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PMID:The protective role of DMBT1 in cervical squamous cell carcinoma. 3140 59