Experimental Study of Malignant Progression and Cell Bioligic Features on Oral Sqamous Cell Carcinoma

MAP激酶家族由一组丝氨酸/苏氨酸激酶组成，它们被细胞外信号激活，并通过质膜上的受体将信号转导到细胞核，在调节许多细胞过程中起着不可或缺的作用。特别是细胞外信号调节蛋白激酶（extracellular signal regulated protein kinase， ERK）被认为位于细胞增殖信号向细胞核的转导通路中，参与细胞转化。事实上，ERK在肿瘤细胞中是组成性表达的。在这里，我们试图研究蛋白激酶的可能激活，特别是属于MAP激酶家族的ERK，它与口腔癌的恶性进展有关。在对博来霉素（BLM）敏感性降低的口腔鳞状细胞癌培养的SCCTF细胞系中，显著高水平的ERK组成性表达。在BLM存在下，这些细胞中的ERK水平不受孵育时间的影响。对于口腔癌活检标本，细胞增殖与ERK水平升高呈正相关。虽然ERK水平与分级或细胞分化没有相关性，但低分化癌中Ki-67阳性细胞的发生率更高，Ki-67和ERK双阳性细胞的发生率也更高。因此，在低分化口腔癌中，ERK表达水平与细胞增殖呈正相关，ERK表达水平与恶性程度更高的肿瘤伴抗肿瘤药物耐药性增加呈正相关。这些正相关可能表明，ERK表达的增加导致细胞周期进程加快，包括诱导DNA合成。我们得出结论，ERK可能在口腔鳞状细胞癌的增殖和恶性进展过程中发挥重要作用。

MAP kinase family consists of a group of serine/threonine kinases that are activated by extracellular signals and play an integral role in regulating many cellular processes by transducing signals via receptors on the plasma membranes to nuclei. In particular, ERK (extracellular signal regulated protein kinase) is considered to be positioned in the transduction pathway of cell proliferation signal to nuclei and contribute to cell transformation. Indeed, ERK is constitutively expressed in neoplastic cells. Here, we attempted to examine the possible activation of protein kinase, especially ERK belonging to a MAP kinase family in association with malignant progression of carcinoma in the oral cavity. In cultured SCCTF cell lines established from squamous cell carcinomas of the oral cavity showing decreased sensitivity to bleomycin (BLM), significantly high ERK levels were constitutively expressed. ERK levels in these cells were not affected by the duration of incubation in the presence of BLM.Regarding biopsy specimens from oral carcinomas, there was a positive correlation between the cell proliferation and elevated ERK levels. Although there was no correlation between the ERK levels and grades or cell differentiation, less differentiated carcinomas tended to show higher incidences of Ki-67 positive cells in the tumor and also higher incidences of double positive cellss for Ki-67 and ERK.Thus, in poorly differentiated oral carcinoma, there was a positive correlation between the levels or ERK expression and cell proliferation, and between the levels of ERK expression and more highly malignant tumor accompanied by increased resistance to antitumor drugs. There positive correlations may indicate that the increased ERK expression led to accelerated cell cycle progression including induction of DNA synthesis. We conclude that ERK may play an important role in the processes of proliferation and malignant progression in squamous cell carcinoma of the oral cavity.