Analysis of Cell Cycle Regulators and Extracellular Matrices Associated with Cell Proliferation in Salivary Gland Tumors

1. 在ACCs中，在各种细胞周期调节因子中，p27的表达降低与ACCs的发生进展关系最为密切，可作为预测转移和预后不良的良好指标。通过ACC细胞系的体外检测表明，翻译后蛋白酶体介导的降解增加可能在降低p27表达中起重要作用。抑制蛋白酶体介导的p27蛋白降解可能成为ACC患者新疗法的可能靶点。Bcl-2和bax在唾液腺肿瘤中有不同程度的表达。Bcl-2在低增殖活性的腺泡细胞癌中强烈表达，提示抑制肿瘤细胞凋亡可能在肿瘤进展中起重要作用。另一方面，高增殖活性的低分化粘液表皮样癌中bax的表达比bcl-2更强烈。3.1)多种糖胺聚糖（glycosaminoglycans, GAGs）存在于上皮区域的小细胞间隙以及PAs的粘液样区或软骨样区，提示其是由实质细胞产生和分泌的。硫酸肝素（HS）在软骨样细胞和部分上皮细胞的细胞核中强烈显示，在肿瘤基质中不存在，而其他gag仅在细胞外基质（ECM）中存在。这些发现表明，HS可能主要与调节细胞生长和分化有关，而不是参与ECM的构成。2)黏液样或软骨样基质中含有多糖和聚集蛋白，而真正的间质基质中含有decorin和PG-M/versican。聚集蛋白是一种主要的蛋白聚糖，可能主要由肿瘤肌上皮细胞产生。3)免疫电镜观察发现，肿瘤肌上皮细胞产生gag和聚集蛋白。少

1. In ACCs, among various cell cycle regulators, the reduced expression of p27 was most closely related with development and progression and it can be a good indicator for predicting metastasis and poor survival. It was indicated that increased proteasome-mediated degradation after translation may play an important role in the reduction of p27 expression on the basis of the examination using ACC cell lines in vitro. Inhibition of proteasome-mediated degradation of p27 protein may be used as a possible target of a novel therapy for ACC patients.2. Bcl-2 and bax were expressed with varying intensity in salivary gland tumors. Bcl-2 was intensely expressed in acinic cell carcinomas with low proliferative activity, suggesting that the inhibition of apoptosis of tumor cells may play an important role in the tumor progression. On the other hand, poorly differentiated mucoepidermoid carcinoma with high proliferative activity expressed bax more intensely than bcl-2. The promotion of apoplosis a … More nd proliferation may simultaneously occur in such highly proliferative tumors.3.1) Various glycosaminoglycans (GAGs) were present at the small intercellular spaces in epithelial areas as well as in myxoid or chondroid areas in PAs, suggesting their production and secretion by the parenchymal cells. Heparan sulfate(HS) was intensely revealed in the nuclei in the chondroid and some epithelial cells and absent from tumor matrices, but other GAGs were only present in the extracellular matrices(ECM). These findings suggest that HS may be mainly related to modulating cell growth and differentiation rather than contributing to ECM constitution.2) Biglycan and aggrecan were contained in myxoid or chondroid matrices, although decorin and PG-M/versican were present in the true mesenchymal stroma. Aggrecan is a major proteoglycan and may be produced mainly by neoplastic myoepithelial cells.3) It was revealed by immuno-electromicroscopic observations that GAGs and aggrecan are produced by the neoplastic myoepithelial cells. Less