• Journal of Life Science
• /
• v.15 no.2 s.69
• /
• pp.231-235
• /
• 2005

Matrix metalloproteinases (MMPs) are a family of structurally and functionally related zinc-dependent enzymes responsible for proteolytic degradation of extracellular matrix components such as base membrane or interstitial stroma. MMPs play an important role in a variety of physiological and pathological tissue remodeling processes, including wound healing, embryo implantation, tumor invasion and metastasis. Since MMP-9 (gelatinase B) has unique ability to cleave type IV collagen, gene expression of MMP-9 has been focused on as a pharmacological target. Flavonoids are a class of compounds that are widely spread in plants. In the coures of screening for the suppressors of MMP-9 gene expression from natural products, Metasequoia glyptostroboides was selected. Six flavonoids, sciadopitysin, isoginkgetin, bilobetin, 2,3-dihydrohinokiflavone, luteolin and apigenin were purified as suppressors of MMP-9 gene expression from M. glyptostroboides. The suppressing activity of the isolated flavinoids on the MMP-9 gene expression was measured by gelatin zymography and Nothern blot analysis.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.2
• /
• pp.189-197
• /
• 2000

Background : Tissue inhibitor of metalloproteinase is a natural inhibitor that counteracts pro teolytic enzymes essential to the invasion of cancer cell. Whether or not TIMP-2 gene transfer via adenovirus could inhibit the invasion of lung cancer cell iη vitro was evaluated for the future purpose of gene therapy against lung cancer. Methods : Recombinant adenovirus-TIMP-2(Ad-TIMP-2) was generated by homologous recombination after pACCMV-TIMP-2 and pJM17 were cotransfected into 293 cell by standard calcium phosphate coprecipitate method. Calu-6, one of the most invasive lung cancer cells, was transduced with Ad-TIMP-2 or Ad-$\beta$gal. Anchorage-independent growth and invasiveness were assessed by soft agar clonogenicity assay and invasion assay using two-chamber, well divided by matrigel. Results : Ad-TIMP-2 transduced calu-6 cells produced biologically active TIMP-2 more than 50 times more than parental calu-6. TIMP-2 gene transfer did not suppress the in vitro tumorigenicity. However, two chamber well assay revealed that Ad-TIMP-2 transduction reduced the invasiveness of calu-6 efficiently (12% compared with parental cell) even at low 10moi. Conclusion : Even though TIMP-2 gene transfer did not inhibit in vitro tumorigenicity, it did inhibit invasion of lung cancer cell in vitro. The inhibition of invasion by Ad-TIMP-2 may be a useful strategy for the treatment of lung cancer.

• Journal of Genetic Medicine
• /
• v.6 no.1
• /
• pp.1-7
• /
• 2009

Epigenetic changes represented by promoter CpG island hypermethylation and histone modification are an important carcinogenetic mechanism, which is found in virtually all histologic types of human cancer. About 60-70% of human genes harbor CpG islands in their promoters and 5' exonal sequences, and some of them undergo aberrant promoter CpG island hypermethylation and subsequent downregulation of gene expression. The loss of expression in tumor suppressor or tumor-related genes results in acceleration of tumorigenic processes. In addition to regional CpG island hypermethylation, diffuse genomic hypomethylation represents an important aspect of DNA methylation changes occurring in human cancer cells and contributes to chromosomal instability. These apparently contrasting methylation changes occur not only in human cancer cells, but also in premalignant cells. CpG island hypermethylation has gained attention for not only the tumorigenic mechanistic process, but also its potential utilization as a tumor biomarker. DNA methylation markers are actively investigated for their potential uses as tumor biomarkers for diagnosis of tumors in body fluids, prognostication of cancer patients, or prediction of chemotherapeutic drug response. In this review, these aspects will be discussed in detail.

• Journal of the Korean Chemical Society
• /
• v.50 no.2
• /
• pp.116-122
• /
• 2006

In this study we extracted DNA from 100 tissues of breast cancer patients and 103 normals. Then we confirmed single-nucleotide polymorphism(SNP) using PCR-DHPLC(polymerase chain reaction-denaturing high performance liquid chromatogrphy).Also, we studied SNP of samples using several columns to identify relation between packing materials of column and resolution.As a result, we identified 4 C/A, C/G genotypes(4%) in exon 5 and 37 T del genotypes(37%) in exon 8 among 100 breast cancer tissues and 2 in exon 5, 9 in exon 8 among 103 normal samples.In resolution test, we confirmed that PS-DVB(poly styrene-divinylbenzen) column is more efficient than C18 column.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.26 no.3
• /
• pp.254-261
• /
• 2000

The present study has attempted to look into the mechanism of ras-induced carcinogenesis in a human epithelial cell system. Human epithelial cells immortalized with Ad12-SV40 hybrid virus were used to assess carcinogenic potential of the ras-oncogene. Cells transfected with pSV2-ras showed characteristics of cellular transformation. The transformation parameters such as cell density, soft-agar colony formation, and cell aggregation were significantly increased in the cells expressing ras oncoprotein. In addition, the duration required for the appearance of foci was shortened in the ras-transfected cells. Consistent with other reports, our results demonstrated an evidence that the ras-oncogene induced the cellular transformation of human epithelial cell system. When a high concentration of glucocorticoid was added into the media, transformation process was accelerated. It is speculated that glucocorticoid may provide an advantageous environment for the proliferation of the transformed cells. The induction of the intracellular free calcium concentrations following agonist treatment was significantly lower in the transformed cells than in the control cells. These effects were more manifested in the presence of extracellular cacium, indicating that the transformation process may alter the influx pathway of extracellular calcium. The induction of $IP_3$ following agonist treatment was also lower in the transformed cells than in the control cells. Thus, it is suggested that phospholipase C-coupled pathway was down-regulated in the process of the ras-induced transformation. While the levels of $TGF-{\beta}_1$ and PAI-2 mRNAs were decreased, the level of fibronectin mRNA was increased. The results indicate that mechanism of the ras-induced transformation may be associated with the altered expressions of growth regulatory factors. The present study demonstrates an evidence that the ras-induced cellular transformation may be associated with alteration of signal transduction and growth regulatory factors. The study will contribute to improve the understanding of molecular mechanism of epithelium-derived cancers including oral cancer.

• Journal of Life Science
• /
• v.32 no.4
• /
• pp.271-278
• /
• 2022

The detailed mechanism by which cancer upregulated gene 2 (CUG2) overexpression induces cancer stem cell-like phenotypes is not fully understood. The downregulation of FBXW7 E3 ligase, a tumor suppressor known for its proteolytic regulation of oncogenic proteins such as cyclin E, c-Myc, Notch, and Yap1, has been frequently reported in several types of tumor tissues, including those in the large intestine, cervix, and stomach. Therefore, we investigated whether FBXW7 is involved in CUG2-induced oncogenesis. In this study, the decreased expression of FBXW7 was examined in human lung adenocarcinoma A549 (A549-CUG2) and human bronchial BEAS-2B cells (BEAS-CUG2) overexpressing CUG2 and compared with control cells stably expressing an empty vector (A549-Vec or BEAS-Vec). Treatment with MG132 (a proteosome inhibitor) prevented the degradation of FBXW7 and Yap1 proteins, which are substrates of the FBXW7 E3 ligase. To address the role of Fbxw7 in the development of cancer stem cell (CSC) phenotypes, we suppressed Fbxw7 protein levels using its siRNA. We observed that decreased levels of FBXW7 enhanced cell migration, invasion, and spheroid size and number in A549-Vec and BEAS-Vec cells. The enforced expression of FBXW7 produced the opposite results in A549-CUG2 and BEAS-CUG2 cells. Furthermore, the downregulation of FBXW7 elevated the activities of EGFR, Akt, and ERK1/2 and upregulated β-catenin, Yap1, and NEK2, while the enforced expression of FBXW7 generated the opposite results. We thus propose that FBXW7 downregulation induced by CUG2 confers CSC-like phenotypes through the upregulation of both the EGFR-ERK1/2 and β-catenin-Yap1-NEK2 signaling pathways.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.26 no.1
• /
• pp.45-52
• /
• 2000

Nowadays, there are a lot of evidence that mutation of the p53 tumor suppressor gene is one of the most common genetic abnormalities in neoplastic progression. In this study, we analyzed 20 specimens of oral tumors(squamous cell carcinoma 14 cases, ameloblastoma 3 cases, adenoid cystic carcinoma 2 cases, malignant schwannoma 1 case)using polymerase chain reaction and direct sequencing which used an automated DNA sequencer and software for detection of mutations. Polymerase chain reactions were performed with 4 sets of primers encompassing exon 5, 6, 7, 8, and direct sequencing method was employed. The results were as followings. 1. We detected 10 point mutations out of 20 specimens (50%). 2. The genetic alterations included 7 mis-sense mutations resulting in single amino acid subtitutions, 2 silent mutations, 1 non-sense mutations encoding a stop codon. 3. Mutations were mostly in exon 7(7 out of 10 mutations, 70%) and involved codons 225, 234, 235, 236, 238, 247. 4. Therse were 4 cases of $T{\rightarrow}A$ transversion, 2 cases of $C{\rightarrow}A$ transversion, $A{\rightarrow}G$ transition, 1 case of $C{\rightarrow}G$, $T{\rightarrow}G$ transversion respectively. 5. We could find out point mutations more conveniently using PCR - Automated Direct Sequencing method.

• Journal of the Korean Society of Radiology
• /
• v.83 no.1
• /
• pp.246-251
• /
• 2022

Li-Fraumeni syndrome (LFS) is an inherited autosomal-dominant tumor-predisposition disorder caused by germline mutations in the TP53 tumor suppressor gene. Since patients with LFS are likely to develop therapy-related cancers, radiation therapy should be avoided if breast cancer is found in these individuals. Herein, we present a case of secondary breast cancer in an LFS patient after radiation and chemotherapy for the first diagnosed breast sarcoma.

• Journal of Life Science
• /
• v.14 no.3
• /
• pp.445-452
• /
• 2004

We investigated the cytotoxic effects of seven furanoterpenoids 〔sarcotin A, epi-sarcotin A, ircinin-1, epi-sarcotrine B, sarcotin I, (8E, l3Z, 20Z)-strobilinin/(7E,l3Z, 20Z)-felixinin and (7E,12E,18R,20Z)-variabilin〕 isolated from the sponge Sarcotragus sp. (the order Dictyoceratida) on the growth of A549 human lung carcinoma cells. MTT data revealed that sarcotin A and (7E,12E,18R,20Z)-variabilin exhibited higher potencies on the anti-proliferative activities than the other compounds in A549 cells. The growth inhibition by treatment with compounds (especially epi-sarcotin A, ircinin-1 and epi-sarcotrine B) were associated with the induction of apoptotic cell death through the concentration-dependent increase of Bax/Bcl-2 ratio in a p53-dependent or independent pathway Additionally, epi-sarcotin A and ircinin-1 strongly inhibited the levels of cyclooxygenase (COX)-2 expression without alteration of COX-1. Taken together, the results suggest that the furanoterpenoids from the marine sponge have strong potentials as candidates for anti-cancer drugs.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.34 no.5
• /
• pp.509-517
• /
• 2008

DNA damage accumulates in cells as a result of exposure to exogenous agents such as benzopyrene, cigarette smoke, ultraviolet light, X-ray, and endogenous chemicals including reactive oxygen species produced from normal metabolic byproducts. DNA damage can also occur during aberrant DNA processing reactions such as DNA replication, recombination, and repair. The major of DNA damage affects the primary structure of the double helix; that is, the bases are chemically modified. These modification can disrupt the molecules'regular helical structure by introducing non-native chemical bonds or bulky adducts that do not fit in the standard double helix. DNA repair genes and proteins scan the global genome to detect and remove DNA damage and damage to single nucleotides. Direct reversal of DNA damage, base excision repair, double strand break. DNA repair are known relevant DNA repair mechanisms. Four different mechanisms are distinguished within excision repair: direct reversal, base excision repair, nucleotide excision repair, and mismatch repair. Genetic variation in DNA repair genes can modulate DNA repair capacity and alter cancer risk. The instability of a cell to properly regulate its proliferation in the presence of DNA damage increase risk of gene mutation and carcinogenesis. This article aimed to review mechanism of excision repair and to understand the relationship between genetic variation of excision repair genes and head and neck cancer.