• International journal of thyroidology
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• v.10 no.2
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• pp.96-101
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• 2017

Background and Objectives: Anaplastic thyroid carcinoma (ATC) is commonly related with concurrent differentiated thyroid carcinoma (DTC). We aimed to examine the clinicopathologic characteristics, prognosis and gene expression of DTC with anaplastic foci. Materials and Methods: Eighteen patients with DTC with anaplastic foci were enrolled in this study. To compare the clinicopathologic characteristics and prognosis of anaplastic foci subjects with conventional ATC or DTC, we additionally included 12 ATC and 1030 DTC patients who diagnosed during same period. Immunohistochemistry was performed to check the gene expression in anaplastic foci and DTC component. Results: In anaplastic foci group, tumor size was larger ($2.5{\pm}1.3$ vs. $1.2{\pm}0.9cm$, p=0.001), distant metastasis was more frequent (11.1 vs. 0%, p=0.000) and 1-year survival rate was low (88.9 vs. 100%, p=0.000) than DTC group. In contrast, compared with ATC group, anaplastic foci group showed younger age at diagnosis ($50{\pm}16$ vs. $63{\pm}18years$, p=0.039), smaller tumor size ($2.5{\pm}1.3$ vs. $3.8{\pm}1.4cm$, p=0.027), less distant metastasis (11.1 vs. 41.7%, p=0.084) and longer 1-year survival rate (88.9 vs. 25.0%, p=0.001). Expression of p53 protein was observed in 100% of anaplastic foci, ATC and 12.5% of papillary thyroid carcinoma component. Conclusion: DTC with foci of anaplastic transformation has a worse prognosis than DTC, but a better prognosis than ATC. Our results support that DTC with anaplastic foci was intermediate state from DTC to ATC.

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

• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.7-13
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• 2009

In this study, we investigated the anti-proliferative effect of Damina 909 in human cancer cell lines and tumor-xenografted nude mice to elucidate its potential in treating many cancers. Damina 909 treatment resulted in inhibition of cell proliferation of human pancreatic cancer cells. Our in vivo study showed that the weight of pancreatic tumors in Damina 909-treated group were the lighter than control group. Consequently, the intake of food and water in Damina 909-treated group did not change, while those in control group were steadily decreased over a period of treatment. Moreover, Damina 909 treatment elevated the protein expression of p53 and p21 in pancreatic tumor of xenografted nude mice. In summary, compare to other human cancer cells such as prostate and hepatocyte, Damina 909 is most effectively inhibited proliferation of pancreatic cancer cells by increasing the expression of tumor suppressor genes. This led us to speculate that a candidate substance for effective cancer therapy of pancreatic cancer might be contained in Damina 909.

• BMB Reports
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• v.57 no.7
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• pp.318-323
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• 2024

Regulation of cell fate and lung cell differentiation is associated with Aminoacyl-tRNA synthetases (ARS)-interacting multifunctional protein 2 (AIMP2), which acts as a non-enzymatic component required for the multi-tRNA synthetase complex. In response to DNA damage, a component of AIMP2 separates from the multi-tRNA synthetase complex, binds to p53, and prevents its degradation by MDM2, inducing apoptosis. Additionally, AIMP2 reduces proliferation in TGF-β and Wnt pathways, while enhancing apoptotic signaling induced by tumor necrosis factor-α. Given the crucial role of these pathways in tumorigenesis, AIMP2 is expected to function as a broad-spectrum tumor suppressor. The full-length AIMP2 transcript consists of four exons, with a small section of the pre-mRNA undergoing alternative splicing to produce a variant (AIMP2-DX2) lacking the second exon. AIMP2-DX2 binds to FBP, TRAF2, and p53 similarly to AIMP2, but competes with AIMP2 for binding to these target proteins, thereby impairing its tumor-suppressive activity. AIMP2-DX2 is specifically expressed in a diverse range of cancer cells, including breast cancer, liver cancer, bone cancer, and stomach cancer. There is growing interest in AIMP2-DX2 as a promising biomarker for prognosis and diagnosis, with AIMP2-DX2 inhibition attracting significant interest as a potentially effective therapeutic approach for the treatment of lung, ovarian, prostate, and nasopharyngeal cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2699-2703
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• 2012

The functional significance of the proteasome activator $REG{\gamma}$ in the regulation of cell proliferation and apoptosis has been recognized. However, pathological contributions to tumor development remain to be elucidated. Both oncogenic proteins and tumor suppressors are targeted by $REG{\gamma}$ for proteasomal degradation. It has been proposed that the role of the $REG{\gamma}$ in the pathogenesis of cancer is cell- and context-specific. In this study, we aimed to explore the potential involvement of $REG{\gamma}$ in laryngeal carcinomas, comparing protein expression in tumor and adjacent tissues by immunohistochemical staining and Western blot analysis. We also characterized the correlation between the expression of $REG{\gamma}$ and the previously identified substrates p53 and p21. We showed that $REG{\gamma}$ was abnormally highly expressed in cancer tissues. Statistical analysis revealed that there was a positive relationship between the level of $REG{\gamma}$ and the expression of p53 and p21. Our study suggests that $REG{\gamma}$ overexpression can facilitate the growth of laryngeal cancer cells.

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

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.297-305
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• 2021

Luteolin, a sort of flavonoid, has been reported to be involved in neuroprotective function via suppression of neuroinflammation. In this study, we investigated the protective effect of luteolin against oxidative stress-induced cellular senescence and its molecular mechanism using hydrogen peroxide (H₂O₂)-induced cellular senescence model in House Ear Institute-Organ of Corti 1 cells (HEI-OC1). Our results showed that luteolin attenuated senescent phenotypes including alterations of morphology, cell proliferation, senescence-associated 𝛽-galactosidase expression, DNA damage, as well as related molecules expression such as p53 and p21 in the oxidant challenged model. Interestingly, we found that luteolin induces expression of sirtuin 1 in dose- and time-dependent manners and it has protective role against H₂O₂-induced cellular senescence by upregulation of sirtuin 1 (SIRT1). In contrast, the inhibitory effect of luteolin on cellular senescence under oxidative stress was abolished by silencing of SIRT1. This study indicates that luteolin effectively protects against oxidative stress-induced cellular senescence through p53 and SIRT1. These results suggest that luteolin possesses therapeutic potentials against age-related hearing loss that are induced by oxidative stress.

• The Journal of Korean Medicine
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• v.25 no.4
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• pp.79-89
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• 2004

Saussurea lappa and Taraxacum mongolicum have been used for herbal medicinal treatments against cancers in East Asia. We performed this study to understand the molecular basis underlying the anti-tumor effects of two herbs and analyzed the effects of these medicinal herbs on proliferation and on expression of cell growth/apoptosis related molecules by using an AGS gastric cancer cell line. The treatments of Saussurea lappa dramatically reduced cell viabilities in a dose and time-dependent manner, but Taraxacum mongolicum did not. FACS analysis and Annexin V staining assay also showed that Saussurea lappa induces apoptotic cell death of AGS. Expression analyses via RT-PCR and Western blots revealed that Saussurea lappa increased expression of the p53 and its downstream effector p21/sup Waf1/, and that the both increased expression of apoptosis related Bax and cleavage of active caspase-3 protein. We also confirmed the translocation of Bax to mitochondria Collectively, our data demonstrate that Saussurea lappa induces growth inhibition and apoptosis of human gastric cancer cells, and these effects are correlated with down- and up-regulation of growth-regulating apoptotic and tumor suppressor genes, respectively.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.3
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• pp.203-212
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• 2020

Promyelocytic leukemia (PML) gene, through alternative splicing of its C-terminal region, generates several PML isoforms that interact with specific partners and perform distinct functions. The PML protein is a tumor suppressor that plays an important role by interacting with various proteins. Herein, we investigated the effect of the PML isoforms on oncostatin M (OSM)-induced signal transducer and activator of transcription-3 (STAT-3) transcriptional activity. PML influenced OSM-induced STAT-3 activity in a cell type-specific manner, which was dependent on the p53 status of the cells but regardless of PML isoform. Interestingly, overexpression of PML exerted opposite effects on OSM-induced STAT-3 activity in p53 wild-type and mutant cells. Specifically, overexpression of PML in the cell lines bearing wild-type p53 (NIH3T3 and U87-MG cells) decreased OSM-induced STAT-3 transcriptional activity, whereas overexpression of PML increased OSM-induced STAT-3 transcriptional activity in mutant p53-bearing cell lines (HEK293T and U251-MG cells). When wild-type p53 cells were co-transfected with PML-IV and R273H-p53 mutant, OSM-mediated STAT-3 transcriptional activity was significantly enhanced, compared to that of cells which were transfected with PML-IV alone; however, when cells bearing mutant p53 were co-transfected with PML-IV and wild-type p53, OSM-induced STAT-3 transcriptional activity was significantly decreased, compared to that of transfected cells with PML-IV alone. In conclusion, PML acts together with wild-type or mutant p53 and influences OSM-mediated STAT-3 activity in a negative or positive manner, resulting in the aberrant activation of STAT-3 in cancer cells bearing mutant p53 probably might occur through the interaction of mutant p53 with PML.

• Journal of the Korean Chemical Society
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• v.47 no.5
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• pp.460-465
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• 2003

Structural alteration of p53 and overexpression of p53 protein are the most common genetic abnormalities in various kinds of human cancer. Mutations in the p53 tumor-suppressor gene are usually associated with an advanced development of colorectal cancer characterized by the transition from the adenoma to carcinoma stage. Mutations in exons 5-8 of the p53 gene were analyzed by the polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) and denaturing high performance liquid chromatography(DHPLC). SSCP analysis detected 7 mutations(C13109>T) in 50 colorectal cancer samples(14%) at exon 5, and DHPLC analysis detected 7 mutations (C13109>T) and 2 mutation(C13202>A, C13204>G) in 50 colorectal cancer samples(18%) at exon 5. All of 9 mutations were proved by sequencing analysis. We conclude that DHPLC is a highly sensitive and specific method for p53 gene mutations.