• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.9
• /
• pp.3723-3727
• /
• 2015

The p53 tumor suppressor protein is a principal mediator of growth arrest, senescence, and apoptosis in response to a broad array of cellular damage. p53 is a substrate for the ubiquitin-proteasome system, however, the ubiquitin-conjugating enzymes (E2s) involved in p53 ubiquitination have not been well studied. UBE2Q1 is a novel E2 ubiquitin conjugating enzyme gene. Here, we investigated the effect of UBE2Q1 overexpression on the level of p53 in the MDA-MB-468 breast cancer cell line as well as the interaction between UBE2Q1 and p53. By using a lipofection method, the p53 mutated breast cancer cell line, MDA-MB-468, was transfected with the vector pCMV6-AN-GFP, containing UBE2Q1 ORF. Western blot analysis was employed to verify the overexpression of UBE2Q1 in MDA-MB-468 cells and to evaluate the expression level of p53 before and after cell transfection. Immunoprecipitation and GST pull-down protocols were used to investigate the binding of UBE2Q1 to p53. We established MDA-MB-468 cells that transiently expressed a GFP fusion proteins containing UBE2Q1 (GFP-UBE2Q1). Western blot analysis revealed that levels of p53 were markedly lower in UBE2Q1 transfected MDA-MB-468 cells as compared with control MDA-MB-468 cells. Both in vivo and in vitro data showed that UBE2Q1 co-precipitated with p53 protein. Our data for the first time showed that overexpression of UBE2Q1can lead to the repression of p53 in MDA-MB-468 cells. This repression of p53 may be due to its UBE2Q1 mediated ubiquitination and subsequent proteasome degradation, a process that may involve direct interaction of UBE2Q1with p53.

• Tuberculosis and Respiratory Diseases
• /
• v.76 no.6
• /
• pp.284-288
• /
• 2014

Malignant mesothelioma (MM) is the aggressive tumor of serosal surfaces. There are crude pathogenetic results regarding the biology of MM. Coordinated upregulations of p53 gene expression are shown in malignancies. We believed that there are changes in the p53 expression with transformation from reactive hyperplasia to MM. A 65-year-old male was admitted the hospital because of left pleuritic chest pains in 2004. Chest computed tomography (CT) results showed left pleural effusions with loculation and pleural thickening. Pathologic findings revealed reactive mesothelial hyperplasia. In 2008, the patient again felt left pleuritic chest pains. Chest CT showed progressive thickening of the left pleura. Pathologic diagnosis was atypical mesothelial hyperplasia. In 2011, chest CT showed progressive thickening of his left pleura. He was diagnosed with well-differentiated papillary mesothelioma. Serial change was analyzed by immunohistochemical staining for p53 of pleural tissues. There were no remarkable changes in p53 expressions during the transformation to MM.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.19
• /
• pp.8069-8073
• /
• 2014

Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, with a high mortality. Most patients present with late stage disease, when the treatment options are limited to systemic chemotherapy. The purpose of our study was to evaluate the significance of p53 and EGFR expression in HCC, and to determine whether these two markers correlate with conventional parameters of prognosis. Materials and Methods: Our study included a total of 45 patients, diagnosed histopathologically with HCC. Clinicopathological data including sex, age, tumor necrosis, tumor size, histologic grading, tumor stage, the presence of cirrhosis and chronic hepatitis, were recorded from the Institute database. Three independent microscopic fields were selected for each sample and all the tumor cells within each microscopic field were counted, and then the positive percent of p53 cells were calculated. Three staining patterns were recognized: diffuse, heterogenous and focal. The intensity of EGFR staining was scored on a scale of 0-3+: 0 no staining; 1+ when a weak membrane staining was observed; 2+ when membrane staining is more intense than in 1+, but less than 3+, and 3+ when intense dark brown staining delineated the membrane. To determine the relationship between EGFR expression and p53, we performed double staining in the same HCC specimens. Results: By immunohistochemical staining, p53 protein was detected in tumor cell nuclei in 20 HCCs (44%). We found a significant correlation between the intensity of p53 expression and the histological grade (p=0.008). EGFR expression was detected in 17 (38%) cases, linked to histological grade (p=0.039). Moreover, the intensity of p53 expression was significantly correlated with EGFR intensity (p=0.014). Conclusions: Our results suggest that overexpression of p53 and EGFR plays an important role in hepatocarcinogenesis and contributes to more advanced disease. These markers are not only valuable predictors of prognosis in HCC, but they are also rational targets for new anti-tumor strategies.

• Korean Journal of Clinical Laboratory Science
• /
• v.52 no.1
• /
• pp.69-77
• /
• 2020

The tumor suppressor gene, p53, is inactivated in the human hepatocellular carcinoma cells line, Hep3B. Berberine has been reported to inhibit the proliferation of cancer cells. This study examined whether apoptosis was induced in berberine-treated Hep3B cells and observed the association between apoptosis and the expression of p53 and DNA methyltransferase (DNMT). The cell viability was measured using an MTT assay. Apoptosis of Hep3B was measured using annexin V flow cytometry. Berberine-treated cells were examined for their DNMT enzymatic activity, mRNA expression, and protein synthesis. The p53 levels were examined by Western blot analysis. The berberine treatment resulted in increased Hep3B cell death and apoptosis in a time- and dose-dependent manner. The DNMT3b activity, mRNA expression, and protein levels all decreased after the berberine treatment. In contrast, the p53 protein levels increased with a concomitant decrease in DNMT3b. No change in the expression of ERK was observed, but the P-ERK levels decreased in a dose dependent manner. These results indicate that a treatment of Hep3B cells with berberine can reduce the expression of DNMT3b, leading to an increase in the tumor suppressant gene p53 and an increase in cell apoptosis. This shows that berberine can effectively suppress the proliferation of liver cancer cells.

• Journal of Nutrition and Health
• /
• v.35 no.1
• /
• pp.53-59
• /
• 2002

Green tea has been recognized as a favorite beverage for centuries in Easter and Westers cultures. Recently, anti-tumor effects of green tea constituents have received increasing attention. However, the mechanism of catechin-mediated cytotoxicity against tumor cells remains to be elusive. To elucidate the mechanical insights of anti-tumor effects, (-)epigallocatechin-gallate(EGCG) of catechin was applied to human lung cancer A549 cells. (-)EGCG induced the death of A549 cells, which was revealed as apoptosis in DNA fragmentation assay. (-)EGCG induced the activation of caspase family cysteine proteases including capase-3, -8 and -9 proteases in A549 cells. Furthermore, (-)EGCG increased the phosphotransferase activity of c-Jun N-terminal kinase 1JNK 1), which further induced tole transcriptional activation of activating protein-1(AP-1) in A549 cells. We suggest that (-)EGCG-induced apotosis of A549 cells is mediated by signaling pathway involving caspase family cysteine protease, JNK1 and transcription factor, AP-1.

• BMB Reports
• /
• v.54 no.7
• /
• pp.335-343
• /
• 2021

Cancer stem cells (CSCs) are a subpopulation of cancer that can self-renew and differentiate into large tumor masses. Evidence accumulated to date shows that CSCs affect tumor proliferation, recurrence, and resistance to chemotherapy. Recent studies have shown that, like stem cells, CSCs maintain cells with self-renewal capacity by means of asymmetric division and promote cell proliferation by means of symmetric division. This cell division is regulated by fate determinants, such as the NUMB protein, which recently has also been confirmed as a tumor suppressor. Loss of NUMB expression leads to uncontrolled proliferation and amplification of the CSC pool, which promotes the Notch signaling pathway and reduces the expression of the p53 protein. NUMB genes are alternatively spliced to produce six functionally distinct isoforms. An interesting recent discovery is that the protein NUMB isoform produced by alternative splicing of NUMB plays an important role in promoting carcinogenesis. In this review, we summarize the known functions of NUMB and NUMB isoforms related to the proliferation and generation of CSCs.

• Genomics & Informatics
• /
• v.13 no.2
• /
• pp.60-67
• /
• 2015

The leading cause of cancer mortality globally amongst the women is due to human papillomavirus (HPV) infection. There is need to explore anti-cancerous drugs against this life-threatening infection. Traditionally, different natural compounds such as withaferin A, artemisinin, ursolic acid, ferulic acid, (-)-epigallocatechin-3-gallate, berberin, resveratrol, jaceosidin, curcumin, gingerol, indol-3-carbinol, and silymarin have been used as hopeful source of cancer treatment. These natural inhibitors have been shown to block HPV infection by different researchers. In the present study, we explored these natural compounds against E6 oncoprotein of high risk HPV18, which is known to inactivate tumor suppressor p53 protein. E6, a high throughput protein model of HPV18, was predicted to anticipate the interaction mechanism of E6 oncoprotein with these natural inhibitors using structure-based drug designing approach. Docking analysis showed the interaction of these natural inhibitors with p53 binding site of E6 protein residues 108-117 (CQKPLNPAEK) and help reinstatement of normal p53 functioning. Further, docking analysis besides helping in silico validations of natural compounds also helped elucidating the molecular mechanism of inhibition of HPV oncoproteins.

• The Korean Journal of Cytopathology
• /
• v.9 no.1
• /
• pp.89-94
• /
• 1998

A case of fine needle aspiration cytology of an osteoclastic giant cell tumor of pancreas, which is an uncommon variant of ductal adenocarcinoma, is described. Aspirated tumor cells were characterized by three populations: (1) bland osteoclast like giant cells with multiple small, round nuclei with distinct nucleoli, and abundant cytoplasm, (2) Individually scattered or loosely clustered medium sized mononuclear tumor cells, having fine chromatin, smooth nuclear membrane, often prominent nucleoli, and high N/C ratio, (3) bland or atypical spindle shaped cells. Osteoid like lacy material was also seen on cell block section. The immunohistochemical studies using paraffin embedded cell block section showed positivities for vimentin and lysozyme in both giant and mononuclear turner cells. However, they were negative for cytokeratin, epithelial membrane antigen, S-100 protein, carcinoembryonic antigen, and p53.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.2
• /
• pp.997-1001
• /
• 2013

Background: Lymphangiogenesis, assessed as lymphovascular density (LVD), is the initial step of generalized tumor lymphovascular invasion (LVI). It also involves VEGF-C as the most important protein family. Lymphangiogenesis among breast cancer cases correlations with several clinicopathological factors are important to determine prognosis and treatment strategies, but results have been controversial and require clarification. Aim: To define correlations between VEGF-C expression, LVD and LVI with several clinicopathological parameters from Indonesian breast cancer patients. Materials and Methods: Using a cross-sectional study, a total of 48 paraffin-embedded tissues of breast cancer from Dr. Sardjito General Hospital Indonesia were assessed for VEGF-C expression, LVD and LVI by immunohistochemistry. Correlations of these markers with clinicopathological parameters like patient age, tumor size, lymph node status, grade, ER/PR and Her-2 status, cell proliferation and p-53 expression were investigated by linear analysis. Correlations of VEGF-C expression and LVI with several clinicopathological parameters were analyzed with Coefficient Contingency Chi-Square test. Results: The mean of patients age was 53.0 year, pre and post-menopausal patients accounting for 56.3% and 43.8%, respectively. Some 10.4% were well, 41.7% moderate and 47.9% poorly differentiated. ER positivity was evident in 50% while PR and Her-2 positivity was found in 31.3% and 33.3%, respectively. Breast cancer cells with over-expression of p-53 was 64.6% and with high cell proliferation was 56.3%. Lymph node metastasis was noted in 63.5%, and LVI in 72.9%. Significant correlations were found between LVD and tumor size (p:0.037), grade (p:0.000), lymphnode status (p:0.036), LVI (p:0.003), as well as with p-53 and cell proliferation. There were also significant correlation of VEGF-C (p:0.011) and LVI (p:0.001) with tumor grade. Only ER status was found to have a correlation with tumor size (p:0.027). Conclusions: This study suggested that in Indonesian breast cancer patients, lymphangiogenesis is correlated with tumor size, grade, lymph node status and tumor lymphovascular invasion, the latter also being related with p-53 over expression and high cell proliferation.

• BMB Reports
• /
• v.52 no.6
• /
• pp.379-384
• /
• 2019

Epithelial-mesenchymal transition (EMT) is widely-considered to be a modulating factor of anoikis and cancer metastasis. We found that, in MDA-MB-231 cells, TP53I11 (tumor protein P53 inducible protein 11) suppressed EMT and migration in vitro, and inhibited metastasis in vivo. Our findings showed that hypoxic treatment upregulated the expression of $HIF1{\alpha}$, but reduced TP53I11 protein levels and TP53I11 overexpression reduced $HIF1{\alpha}$ expression under normal culture and hypoxicconditions, and in xenografts of MDA-MB-231 cells. Considering $HIF1{\alpha}$ is a master regulator of the hypoxic response and that hypoxia is a crucial trigger of cancer metastasis, our study suggests that TP53I11 may suppress EMT and metastasis by reducing $HIF1{\alpha}$ protein levels in breast cancer cells.