• Molecules and Cells
• /
• v.39 no.12
• /
• pp.877-887
• /
• 2016

Tazarotene-induced gene 1 (TIG1) is a retinoic acid-inducible protein that is considered a putative tumor suppressor. The expression of TIG1 is decreased in malignant prostate carcinoma or poorly differentiated colorectal adenocarcinoma, but TIG1 is present in benign or well-differentiated tumors. Ectopic TIG1 expression led to suppression of growth in cancer cells. However, the function of TIG1 in cell differentiation is still unknown. Using a yeast two-hybrid system, we found that transmembrane protein 192 (TMEM192) interacted with TIG1. We also found that both TIG1A and TIG1B isoforms interacted and co-localized with TMEM192 in HtTA cervical cancer cells. The expression of TIG1 induced the expression of autophagy-related proteins, including Beclin-1 and LC-3B. The silencing of TMEM192 reduced the TIG1-mediated upregulation of autophagic activity. Furthermore, silencing of either TIG1 or TMEM192 led to alleviation of the upregulation of autophagy induced by all-trans retinoic acid. Our results demonstrate that the expression of TIG1 leads to cell autophagy through TMEM192. Our study also suggests that TIG1 and TMEM192 play an important role in the all-trans retinoic acid-mediated upregulation of autophagic activity.

• Development and Reproduction
• /
• v.19 no.4
• /
• pp.227-234
• /
• 2015

The objective of this study was to investigate the expression of bovine luteum expressed sequence tags (ESTs), vascular endothelial growth factor (VEGF), and tumor necrosis factor receptor 1 (TNFR1) and the presence of functional ESTs in the bovine corpus luteum (CL) during different stages of the estrus cycle. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed a difference in the expression of ESTs during the CL stage. Concentration of ESTs in the CL tissue increased significantly from the mid-luteal stage and decreased thereafter. RT-PCR analysis showed higher levels of the EST genes in the CL of the mid-luteal stage than in other stages, and the same level of expression of VEGF. Immunohistochemistry analysis of the tissue from CL formation to regression showed low cytosol and aggregation of the nucleus. And activity caspase 3 (apoptosis detector) was most strongly detected in the CL1 stage of bovine. During the estrous cycle, the cytosol was magnified and differentiation of the nucleus was clearly manifested. The ESTs affected the CL, and the relationship between VEGF and TNFR1 played a pivotal role for CL development and activation, dependent on the stage of CL. These results suggest local production of ESTs, the presence of functional ESTs in the bovine CL, and that ESTs play a role in regulating the function of cell death in bovine CL.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.37 no.2
• /
• pp.97-108
• /
• 2011

Cancer stem cells have stem cell-like features, such as the ability for self-renewal and differentiation but show unlimited growth because they have the lost normal regulation of cell growth. Cancer stem cells and normal stem cells have similar features. They show high motility, diversity of progeny, robust proliferative potential, association with blood vessels, immature expression profiles, nestin expression, epidermal growth factor (EGF)-receptor expression, phosphatase and tensin homolog (PTEN) expression, hedgehog pathway activity, telomerase activity, and Wnt pathway activity. On the other hand, with cancer cells, some of these signaling pathways are abnormally modified. In 1875, Cohnheim suggested the concept of cancer stem cells. Recently, evidence for the existence of cancer stem cells was identified. In 1994, the cancer stem cells' specific cell surface marker for leukemia was identified. Since then, other specific cell surface markers for cancer stem cells in solid tumors (e.g. breast and colon cancer) have been identified. In oral cancer, studies on cancer stem cells have been performed mainly with squamous cell carcinomas. Oral cancer specific cell surface markers, which are genes strongly expressed in oral cancer and cancer stem cell specific side populations, have been identified. Cancer stem cells are resistant to radiotherapy and chemotherapy. Therefore, to eliminate malignant tumors efficiently and reduce the recurrence rate, therapy targeting cancer stem cells needs to be performed. Currently, studies targeting the cancer stem cells' specific signaling pathways, telomerase and tumor vasculatures are being done.

• Journal of Yeungnam Medical Science
• /
• v.19 no.2
• /
• pp.116-125
• /
• 2002

Background: In patients with endometrial carcinoma, preoperative evaluation of exact staging has important prognostic and therapeutic implications. The incidence of pelvic and aortic lymph node involvement in endometrial carcinoma depends on grade of tumor differentiation and depth of myometrial invasion. Material and method: To evaluate whether MRI provides a preoperative assessment for staging of endometrial carcinoma, MRI was undertaken in 28 patients, a few weeks before operation. Myometrial invasion was devided in three categories, and involvement of cervix, adnexa, and pelvic cavity were classified. Results: The results of MR imaging were compared with these of pathology. The preoperative MRI staging of endometrial carcinoma was correct in 22 out of 28 patients. In the evaluation of myometrial invasion, the MR imaging underestimated in 4 cases and overestimated in 1 case. Conclusion: In patients with endometrial carcinoma, MR imaging is very useful in the assessment of the depth of myometrial invasion, stromal invasion of cevix, lymphatic & pelvic metastases and extent of the lesion.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.32 no.4
• /
• pp.352-359
• /
• 2006

MMP-2 and MMP-9, type IV collagenases which degrade basement membrane, have been known to play important roles in invasion and metastasis of tumor cells, In addition, they seem to be involved in cell differentiation, apoptosis, angiogenesis and immunity, etc. We immunohistochemically examined epithelial and stromal expressions of MMP-2 and MMP-9 in irritation fibroma, oral leukoplakia, and oral squamous cell carcinoma (OSCC) and have some results as follows: 1. Irritation fibromas, oral leukoplakias and OSCCs mostly showed increased expression of MMP-2 and MMP-9 in the epithelium and connective tissue compared with normal mucosa. 2. There was a significant difference in the epithelial expression of MMP-2 and MMP-9 between irritation fibroma and oral leukoplakia. 3. There was a significant difference in the epithelial and stromal expression of MMP-2 and MMP-9 between irritation fibroma and OSCC. 4. There was a significant difference in the stromal expression of MMP-9 between oral leukoplakia and OSCC. We concluded that rritation fibroma, oral leukoplakia and OSCC have somewhat different characteristics of MMP-2 and MMP-9 expressions, which perhaps result from different pathogenesis.

• Journal of Periodontal and Implant Science
• /
• v.35 no.3
• /
• pp.675-685
• /
• 2005

Bone resorption involves sequential stages of osteoclast precursor migration and differentiation of osteoclast precursors into multinucleated osteoclasts. Stromal cell derived factor (SDF)-1 is a chemotactic factor for osteoclast precursor migration. Matrix metalloproteinase (MMP)-9 is involved in migration of osteoclast precursors and activation of $interleukin(IL)-1{\beta}$. Alveolar bone destruction is a characteristic feature of periodontal disease. Treponema lecithinolyticum is a oral spirochete isolated from the periodontal lesions. The effect of lipopolysaccharide(LPS) from T. lecithinolyticum on expression of SDF-1 and MMP-9 was examined in cocultures of bone marrow cells and osteblasts derived from mouse calvariae. T. lecithinolyticum LPS increased expression of MMP-9 in the coculture. Polymyxin B, an inhibitor of LPS, abolished the increase of MMP-9 mRNA expression by LPS. LPS did not increase the expression of SDF-1, $IL-1{\beta}$ and tumor necrosis $factor(TNF)-{\alpha}$ mRNA in cocultures. Prostaglandin $E_2(PGE_2)$ up-regulated the expression of MMP-9 and NS398, an inhibitor of $PGE_2$ synthesis, down-regulated the induction of MMP-9 expression by T. lecitbinolyticm LPS. These results suggest that T. lecitbinolyticm LPS increases MMP-9 expression in bone cells via $PGE_2$ and that the induction of MMP-9 expression by T. lecitbinolyticm LPS is involved in alveolar bone destruction of periodontitis patients by the increase of osteoclast precursor migration and the activation of bone resorption-inducing cytokine.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.36 no.2
• /
• pp.145-150
• /
• 2010

Anoectochilus formosanus, commonly known as "Jewel Orchids", which has been used in traditional folk medicines for feber, pain, and diseases of the lung and liver in Taiwan. We artificially cultured Anoectochilus formosanus plantlet by using the bioreactor culture system for this study from Anoectochilus formosanus. Previously, several studies have been reported on pharmacological activities of lipid-metabolism, hepatoprotective activity, anti-tumor activity and immuno-stimulating effects but other efficacy were not well known as a cosmetic ingredient for skin care. In this study, we investigated the effect of melanogenesis in B16 mouse melanoma cells and lipid droplet accumulation in 3T3-L1 preadipocytes about Anoectochilus formosanus plantlet extract. We report that Anoectochilus formosanus plantlet extract inhibits the cytoplasmic lipid droplet accumulation through adipogenic differentiation of preadipocytes as well as inhibition of tyorsinase activity and melanogenesis. As a result, our findings indicate that Anoectochilus formosanus plantlet extract may be the potential natural ingredient for whitening and slimming cosmetic products.

• Molecules and Cells
• /
• v.40 no.1
• /
• pp.45-53
• /
• 2017

Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of ${\beta}-catenin$, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was considered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient's age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.

• Journal of Gastric Cancer
• /
• v.10 no.3
• /
• pp.91-98
• /
• 2010

Purpose: Silent mating-type information regulation 2 homologue 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. SIRT1 plays an important role in the regulation of cell death/survival and stress response in mammals. The aim of this study was to investigate whether the SIRT1 gene is involved in the development or progression of gastric cancers. Materials and Methods: SIRT1 and p53 genes in 86 gastric cancers were examined for genetic alterations by PCR-single strand conformation polymorphism sequencing, as well as SIRT1 protein expression in 170 gastric cancers by immunohistochemistry. Results: In the genetic analysis, we found SIRT1 and p53 mutations in two and 12 cases, respectively. Two missense mutations, c.599 C>T (T200I) and c.1258 G>A (E420K), were detected in the SIRT1 gene coding region. The SIRT1 and p53 mutation were found in mutually exclusive gastric cancers. The immunohistochemistry revealed that SIRT1 overexpression was found in 95 (55.9%) of 170 gastric cancers. Altered SIRT1 expression was not statistically associated with clinicopathological parameters, including tumor differentiation, location, lymph node metastasis, or p53 expression. Two cases with an SIRT1 mutation showed increased SIRT1 expression. Conclusions: These results suggest that genetic alterations and overexpression of the SIRT1 gene may contribute to gastric cancer development.

• Archives of Pharmacal Research
• /
• v.22 no.3
• /
• pp.243-248
• /
• 1999

Sialic acids are key determinants for biological processes, such as cell-cell interaction and differentiation. Sialyltransferases contribute to the diversity in carbohydrate structure through their attachment of sialic acid in various terminal positions on glycolipid and glycoprotein (N-linked and O-linked) carbohydrate groups. Gal$\beta$ 1,3(4)GlcNAc $\alpha$2,3-sialyltransferase (ST3Gal III) is involved in the biosynthesis of $sLe^{X}$ and sLe^{a}$ known as selection ligands and tumor-associated carbohydrate structures. The appearance and differential distribution of ST3Gal III mRNA during mice embryogenesis [embryonic (E) days; E9, E11, E13, E15] were investigated by in situ hybridization with digoxigenin-labeled RNA probes coupled with alkaline phosphatase detection. On E9, all tissues were positive for ST3Gal III mRNA expression whereas ST3Gal III mRNA on E11 was not detected throughout all tissues. On E13, ST3GAl III mRNA was expressed in different manner in various tissues. In this stage, ST3Gal III mRNA was positive only in the liver, pancreas and bladder. On E15, specific signal for ST3GAl III was detected in the liver, lung and forebrain. These results indicate that ST3Gal III is differently expressed at developmental stages of mice embryo, and this may be importantly related with regulation of organogenesis in mice.