• Journal of Life Science
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• v.30 no.12
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• pp.1092-1100
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• 2020

The six-transmembrane epithelial antigen of prostate 4 (Steap4) is a metalloreductase that plays a role in intracellular iron and cupper homeostasis, inflammatory response, and glucose and lipid metabolism. Previously, Steap4 has been reported to stimulate adipocyte differentiation; however, the underlying mechanisms of this action remain unexplored. In the present study, we investigated the molecular mechanisms involved in Steap4-induced adipocyte differentiation using 3T3-L1 cells, immortalized brown adipocyte (iBA) cells, and mouse embryonic fibroblast C3H10T1/2 cells. The knockdown of Steap4 using adenovirus-containing shRNA attenuated mitotic clonal expansion (MCE), as evidenced by the impaired proliferation of 3T3-L1 cells, iBA cells, and C3H10T1/2 cells within 48 hr after adding the differentiation medium. Steap4 knockdown downregulated G1/S phase transition-related cell cycle regulators (including cyclin A and cyclin D) and upregulated cell cycle inhibitors (including p21 and p27). Furthermore, Steap4 knockdown inhibited the phosphorylation of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and Akt. Moreover, Steap4 knockdown repressed the expression of early adipogenic activators, such as CCAAT-enhancer-binding protein β (C/EBPβ) and Kruppel-like factor family factor 4 (KLF4). On the other hand, Steap4 knockdown stimulated the expression of adipogenic inhibitors, including KLF2, KLF3, and GATA2. The overexpression of Steap4 using an adenovirus removed the repressive histone marks H3K9me2 and H3K9me3 on the promoter of C/EBPβ. These results indicate that Stepa4 stimulates adipocyte differentiation through the induction of MCE and the modulation of early adipogenic transcription factors, including C/EBPβ, during the early phase of adipocyte differentiation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.6
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• pp.535-542
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• 2001

The purpose of this study was to examine the mRNA levels of TNF-${\alpha}$ and IL-6 in the cell lines of normal oral keratocyte and oral squamous cell carcinoma. Total RNA was extracted from these cell lines, observed under UV light, developed by radiographic films of PCR products via reverse transcriptase polymerase chain reaction(RT-PCR) amplication, and measured with densitometer. Each mRNA level of these cell lines divided by ${\beta}$-actin mRNA level was compared to that of normal control group. The results were as follows: 1. Higher mRNA expression of TNF-${\alpha}$ than IL-6 in the normal oral epithelial cell line. 2. In general, expression of mRNA of IL-6 appeared 3-4 times more in tumor cell lines than in control group. 3. mRNA expression of TNF-${\alpha}$ showed variable expression in tumor cell lines, unlike normal cell line. 4. There are no special connections between differentiation of oral cancer cell lines and mRNA expression of TNF-${\alpha}$ and IL-6. From the above results, expression of mRNA of IL-6 in the cell lines of squamous cell carcinoma used in this study has higher than the normal oral epithelial cell line, but there are no relationship between the differentiation of oral cancer cell lines and the expression of mRNA of TNF-${\alpha}$ and IL-6.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5883-5890
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• 2013

Previously, we demonstrated overexpression of semaphorin4D (SEMA4D, CD100) to be closely related to tumor angiogenesis in epithelial ovarian cancers (EOCs). However, the function and expression of SEMA4D in the EOC microenvironment has yet to be clarified in detail. In this study, we confirmed that overexpression of SEMA4D in primary tumors and ascites was related to low differentiation, platinum resistance and a refractory status (P<0.05), while high M2 macrophage count and percentage were evident in EOC patients with advanced FIGO stage and platinum resistance (P<0.05), using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and fluorescence-activated cell sorting (FACS), respectively. The data showed correlations of SEMA4D expression and M2 macrophage counts in primary tumors and M2 macrophage percentage in ascites (r=0.281 and 0.355, each P<0.05). In the Cox proportional hazard mode, SEMA4D expression was an independent indicator of overall survival (OS) and progression-free survival (PFS) for EOC patients. Furthermore, higher expression of SEMA4D in ovarian cancer cell lines (SKOV3, A2780, and SW626) and their supernatants were found than that in a human primary cultured ovarian cell and its supernatant by reversed transcript PCR (RT-PCR), Western blotting and ELISA, respectively. Interestingly, peripheral blood monocytes (MOs) tended towards the M2-polarized macrophage phenotype ($CD163^{high}$) in vitro after human recombined soluble SEMA4D protein stimulation. These findings suggest that SEMA4D might possibly serve as a reliable tool for early and accurate prediction of EOC poor prognosis and could playan important role in promoting tumor dissemination and metastasis in the EOC microenvironment. Thus SEMA4D and its role in macrophage polarization in EOC warrants further study.

• The Korean Journal of Zoology
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• v.33 no.1
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• pp.78-93
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• 1990

The ultrastructure of epididymal epithelium of 10, 20, 35 and 80 day-old mouse was observed to study the differentiation and function of the epithelial cells in connection with the absorption and secretion during sexual matruation. The differentiation of epididymis was divided into three phases of, 1) undiflerentiated phase until the day 20 after birth, 2) growing and differentiating phase between the day 20 and 35, and 3) maturating phase up to the adult. Each phase was closely related with the lumination of seminiferous tubule and the influx of spermatozoa within testicular fluid from testis. In adult, the ultrastructural features appeared an absorptive function in the principal cells of proximal caput epididymis, and a strong activity of protein synthesis and secretion in distal caput, corpus and cauda epididymis. Clear cells were predominantly located in corpus and cauda epidiymis, and plenty of absorption vesicles including membranous particles assumed to be the cellular residues from spermatozoa were observed at apical region. Therefore, the distribution of various cell types of epithelium and the ultrastructure even in the same type of epithelial cell, were different according to the epididymal regions.

• The Korean Journal of Zoology
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• v.39 no.1
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• pp.54-64
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• 1996

Normal development of the olfactory placode was studied to describe the sequence of events involved in the development of the olfactory placode. It has been primarily concerned with the morphological differentiation of the sensory neurons, their initial growth, maturation patterns and the contacts of their axons with the primitive prosencephalic vesicle. The olfactory organ first appears at stage 23 as a paired thickening of the two ectodermal layers: the superficial non-nervous layer (NNL) and the inner nervous layer (NL). Receptor cells differentiate from the NL and the supporting cells develop from the NNL. After stage 26 the placodal cells begin to migrate toward the epithelial surface between the NNL cells and their apical processes reach the surface at stage 28. As the apical process reaches the epithelial surface, basal processes (presumptive axons) sprout from the base of the NL cells at stage 29/30. They penetrate the underlying telencephalon by stage 32. Sensory synaptic contacts first appear at stage 37/38. Some placodal cells remain at the olfactory epithelium as basal cells while other placodal cells differentiate into olfactory neurons. The results confirmed that neurons originate exclusively from the nervous layer of the ectoderm while supporting cells originate from the NNL layer. The results also indicate that the development of olfactory neuron is independent of information from the target ftssue.

• Toxicological Research
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• v.22 no.3
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• pp.283-291
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• 2006

The survival and growth of epithelial cells depends on adhesion to the extracellular matrix. An adhesion signal may regulate the initiation of differentiation, since epidermal keratinocytes differentiate as they leave the basement membrane. A metabolically dead cornified cell envelope is the end point of epidermal differentiation so that this process may be viewed as a specialized form of programmed cell death. In order to investigate the precise cellular signaling events loading to terminal differentiation of keratinocytes, we have utilized HaCaT cells to monitor the biological consequences of $Ca^{2+}$ stimulation and numerous downstream signaling pathways, including activation of the extracellular signal-regulated protein kinase(ERK) pathway and activation of phosphatidylinositol 3-kinase(PI3K). The results presented in this study show that $Ca^{2+}$ function as potent agents for the differentiation of HaCaT keratinocytes, and this differentiation depends or the activation of ERK, Protein kinase B(PKB) and p70 ribosomal protein S6 kinase(p70S6K). Finally, the results show that the expression of Activator protein 1(AP-1; c-Jun and c-Fos) increased following $Ca^{2+}$-mediated differentiation of HaCaT cells, suggesting that ERK-mediated AP-1 expression is critical for initiating the terminal differentiation of keratinocytes.

• Development and Reproduction
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• v.17 no.3
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• pp.215-220
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• 2013

Recently, the RNA/DNA-binding protein FUS, Fused in sarcoma, was shown to play a role in growth, differentiation, and morphogenesis in vertebrates. Because little is known about Fus, we investigated its expression pattern in murine tooth development. In situ hybridization of mouse mandibles at specific developmental stages was performed with a DIG-labeled RNA probe. During early tooth development, Fus was detected in the dental epithelium and dental mesenchyme at 11 days postcoitum (dpc) and 12 dpc. From 14 dpc, Fus was strongly expressed in the dental papilla and the cervical loop of the dental epithelium. At postnatal day 4 (PN4), Fus expression was observed in the odontoblasts, ameloblasts, the proliferation zone of the pulp, and the cervical loop. At PN14, the expression pattern of Fus was found to be maintained in the odontoblasts and the proliferation zone of the pulp. Furthermore, Fus expression was especially strong in the Hertwig's epithelial root sheath (HERS). Therefore, this study suggests that Fus may play a role in the HERS during root development.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.3
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• pp.211-220
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• 2007

Objective: In organotypic culture of immortalized human oral keratinocytes (IHOK), the change of the growth and differentiation was investigated according to the fibroblast type and the involvement of mitogen-activated protein (MAP) kinase. Materials & Methods: IHOK was cultured three dimensionally with gingival fibroblast (GF), dermal fibroblast (DF) and immortalized gingival fibroblast (IGF). We characterized biologic properties of three dimensionally reconstructed IHOK by histological, immunohistochemical, and Western blot analysis. We also investigated whether MAP kinase pathway was involved in epithelial-mesenchymal interaction by Western blot analysis. Results: The best condition of three dimensionally cultured IHOK was the dermal equivalent consisting of type I collagen and IGF. IGF increased the expression of more proliferating cell nuclear antigen (PCNA), involucrin than GF and DF in response to co-culture with IHOK. Extracellularly regulated kinase (ERK) pathway was activated in organotypic co-culture with IGF. Conclusion: The organotypic co-culture of IHOK with dermal equivalent consisting of type I collagen and IGF resulted in excellent morphologic and immunohistochemical characteristics and involved ERK pathway. The epithelial-mesenchymal interaction was activated according to the fibroblast type.

• Asian-Australasian Journal of Animal Sciences
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• v.17 no.4
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• pp.453-459
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• 2004

Chick embryos from stage 14 to stage 31 were studied by means of serial section and light microscopy in order to learn the relationship between the settlement sites of the primordial germ cells (PGCs) and the forming genital ridge. The results showed that: when embryo hatched for 53-56 h, the PGCs reached the coelomic epithelial tissue where gonad would be formed, meanwhile the epithelial tissue began thicker before the PGCs reached. Before stage 19, the final region the PGCs arrived was the thickened portion of the coelomic epithelium, the glycogen in the PGCs cytoplasm maintenance remained unchanged. However at the 3.5-5th hatching day, the glycogen in the PGCs cytoplasm reduced gradually. On the 6th hatching day, the gonad of the embryo appeared the feature of ovary, and the glycogen in the PGCs cytoplasm reduced further. On the 7th hatching day, the differentiation of ovary or testis was obvious and the glycogen in the PGCs cytoplasm later disappeared.

• Journal of Periodontal and Implant Science
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• v.27 no.1
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• pp.111-116
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• 1997

The oral cavity is easily accessible for direct exposure of a malignant disease. 1 percent of the oral malignant tumors are of metastatic origin and approximately 10 percent to 25 percent of the 1 percent fraction originate from the lungs. A case of metastatic lung carcinoma to the gingiva in a 88-year-old male is reported. He complained of pain and swelling between right maxillary 1st premolar and 2nd molar. Although surgical excision of the lesion has been done, the gingival lesion developed as a quickly growing mass and recurred 2 weeks after surgical excision. The gingival mass was histopathologically diagnosed as an undifferentiated carcinoma. Epithelial layer was continuous without ulceration and it seems that the cancer cells are originated from primary tumor. Infiltrated cancer cells were pleomorphic and dyskeratotic. The cells had 2 or more nuclei, not showing squamous or glandular differentiation. Immunohistochemical study revealed the cells originated from the epithelial cells. The prognosis is poor, because prognosis depends on surgical elimination of the primary tumor.