A poor prognosis of oral squamous cell carcinoma (SCC) is partly due to the invasiveness and metastasis of the tumor. One of key elements in tumor invasion and metastasis in the degradation of extracellular matrix is tissue inhibitors of metalloproteinases (TIMPs). This study was performed to determine the expression of TIMP-1 and TIMP-2 of oral SCCs with regard to the histologic invasiveness and differentiation in 5 normal oral mucosa and 36 oral SCCs. The histologic invasiveness of oral SCCs were classified into 4 grades. The differentiation of oral SCCs was divided into 3 grades. The StreptAvidin-Biotin immunohistochemical process, using TIMP-1 and TIMP-2 monoclonal antibodies, was performed to determine the expression of TIMP-1 and TIMP-2. The expression of TIMP-1 was positive in 5 of 17 oral SCCs with weak invasiveness and was positive in 8 of 19 oral SCCs with strong invasiveness. The TIMP-1 expression did not increase significantly with respect to the invasiveness of oral SCCs (P>0.05). The expression of TIMP-2 was strongly positive in 5 out of 17 SCCs with weak invasiveness and was strongly positive in 15 of 19 SCCs with strong invasiveness. The TIMP-2 expression increased significantly with respect to the invasiveness of oral SCCs; the stronger the expression, the stronger the invasiveness (P<0.05). The expression of TIMP-1 and TIMP-2 did not increase significantly with respect to the histologic differentiation. We concluded that with respect to the invasiveness, the TIMP-2 expression increases significantly in oral SCCs but the TIMP-1 expression does not; and that with respect to the histologic differentiation, their expressions do not increase significantly. These results suggested that TIMP-2 can be used as a tool to evaluate the invasiveness of oral SCCs.

The objective of this study was to analyzed pattern of proteins expression abnormally in cloned bovine placenta. TIMP-2 protein whose function is related to extracellular matrix degradation and tissue remodeling processes was one of differentially up-regulated proteins in SCNT placenta. And one of down-regulated protein in SCNT placenta was identified as vimentin protein that is presumed to stabilize the architecture of the cytoplasm. The expression patterns of these proteins were validated by Western blotting. To evaluate how regulatory loci of TIMP-2 and vimentin genes was programmed reprogramming in cloned placenta, the status of DNA methylation in the promoter region of TIMP-2 and vimentin genes was analyzed by sodium Bisulfite mapping. The DNA methylation results showed that there was not difference in methylation pattern of TIMP-2 and vimentin loci between cloned and normal placenta. Histone H3 acetylation state of the nucleosome was analyzed in the cloned placental and normal placenta by Western blotting. A small portion of the protein lysates were subjected to Western blotting with the antibodies against anti acetyl-Histone H3. Overall histone H3 acetylation state of SCNT placenta was significantly higher than those of normal placenta cells. It is postulated that cloned placenta at the end of gestation seems to be unusual in function and morphology of placenta via improper expression of TIMP-2 and vimentin by abnormal acetylation states of cloned genome.

Extensive oral mucosa loss from a variety of conditions is associated with significant functional morbidity and mortality. Although it is known that keratinocytes are a rich source of wound healing promoting factors such as transforming growth factor-β1(TGF-β1), it is not clear whether differentiated keratinocytes in a multi-layer form release this multi-functional growth factor. This study examined the hypothesis that keratinocytes in mono- and multi-layer forms expressed different levels of TGF-β1. When NHOK reached confluency in serum free medium(KBM), in test medium containing 1.2 mM Ca++ KBM NHOK were allowed to form multi-layers and differentiate. The purpose of this study were to investigate the mRNA level of TGF-β1, FGF-2, and TIMP-1 by RT-PCR analysis and also to evaluate the expression of TGF-β1 and involucrin in keratinocytes at different times of the onset of differentiation. The numbers and sizes of these nodules were increased as the process of keratinocyte differentiation proceed. Cultured NHOK in preconfluency under KBM medium expressed a significantly higher level of TGF-β1 relative to those grown in multi-layer forms, while the level of TGF-β1 mRNA gradually reduced to its lowest level at 7 days of growing cells in test medium. Cultured NHOK in preconfluency of KBM medium expressed a lower level of FGF-2 and TIMP-1 relative to those grown in multi-layer forms, while the level of FGF-2 and TIMP-1 mRNA showed the highest level at 3 days at gradually reduced to its lowest level at 7 days of growing cells in test medium. As a differentiation marker for keratinocytes at different time points, the highest level of involucrin mRNA expression was found at the later stage of cell differentiation. It suggested that the expression of TGF-β1 mRNA be consistent with the expression of FGF-2 and TIMP-1 mRNA in NHOK grown in high calcium medium during the terminal differentiation. But differentiated NHOK expressing higher involucrin mRNA could show constant espression of TGF-β1, FGF-2 and TIMP-1.

Matrix metalloproteinases(MMPs) are involved in the degradation of extracellular matrix, which is re lated to infiltrative growth and metastasis of tumor and are regulated by tisslle inhibitor of metalloproteinases(TIMPs) or cell adhesion molecllles such as E-cadherin and epidermal growth factor receptor (EGFR). The aim of this study is to evaluate the relationship between MMP-2, MMP-9 expressions and clinico-pathologic factors, 끼MP-1 ， TIMP-2, EGFR and E-cadherin expressions. lmmunohistochemical stains were perfom1ed on 55 cases of squamous cell carcinoma of the ordl cavity and the results were as follows. MMP-2 and MMP-9 expressions were noted in 30(54.5%) and 22(40.0%) of 55 cases, TIMP-1 and πMP-2 in 21(38.2%) and 33(60.0%), and E-cadherin and EGFR expressions in 35(63.6%) and 26(47.3%) of 55 cases, respectively. MMP-2 expression rdte was slightly higher 띠 cases without recurrence, and 끼MP- 2 expression rate was slightly higher in cases showing more inftltrative growth pattem. 까1e expression rate of EGFR was higher in cases with well differentiation(p=0.OO47), but no posi디ve relationship between the expression rate of Ecadherin and histologic grade was found. Cases with positive reaction for MMP-9 showed an increasing tendency of nega디ve reaction for TIMP-1. π1e expression rate of MMP-2 was higher in cases with positive reaction for E-cadherin and EGFR with no statistical significance. 까1e expression rate of MMP-9 was significantly higher in cases with positive reaction for E-cadherin(p=0.022l). These results suggest that MMP-2, MMP-9, TIMP-1 and TIMP-2 expressions are involved in the development of oral squamous cell carcinomas, but MMP-2, MMP-9, 끼MP-1 ， and 끼MP-2 expressions might not seem to be a useful prognostic factors because there were no significant relationship between clinicopathologic parameters. EGFR expression showed positive correlation with low histologic grade, so EGFR expression could be regarded as a good prognostic factor. In the progression of sqllamous cell

In the expansion of odontogenic cyst, degradation of extracellular matrix and resorp디on of bone are accompa띠ed ， but its mechanism is under debate. The degrees of inflammation and fibrosis were graded in 39 cases of odontogenic cysts. Cytoplasrnic expressions in various cell types according to them were analyzed using immunohistochemis띠， for MMPs and πMPs. In epithelial cells, MMP-2 expression was increased with marked fibrosis(p=O.018) and in stromal cells, MMP-2,-9 and TIMP-2 expressions were slightly higher in cases with mild inflammation and marked fibrosis. Tendencies of positive correlation were found between MMP-2,-9 and TIMP-2 expressions in epithelial cells and between MMP-l and MMP-9 expressions in stromal cells. These results suggest that MMP-l ,-2 ,-9 and TIMP-2 expression might be related to the expansion of odontogenic cysts, and the expression rate of them was different according to cell types and the degree of inflammation and fibrosis.